Matrine reverses the resistance of Haemophilus parasuis to cefaclor by inhibiting the mutations in penicillin-binding protein genes (ftsI and mrcA).

Introduction: Matrine (MT) is a potential resistance reversal agent. However, it remains unclear whether MT can reverse the resistance of Haemophilus parasuis (H. parasuis) to ß-lactams, and, if so, by what mechanism MT works. Methods: We screened one cefaclor (CEC)-resistant strain (clinical strain C7) from eight clinical (H. parasuis) strains and determined the underlying resistance mechanism. Then, we investigated the reversal effect of MTon the resistance of this strain to CEC. Results and Discussion: The production of ß-lactamase, overexpression of AcrAB-TolC system, and formation of biofilm might not be responsible for the resistance of clinical strain C7 to CEC. Fourteen mutation sites were found in four PBP genes (ftsI, pbp1B, mrcA, and prcS) of clinical strain C7, among which the mutation sites located in ftsI (Y103D and L517R) and mrcA (A639V) genes triggered the resistance to CEC. The minimum inhibitory concentration (MIC) of CEC against clinical strain C7 was reduced by two to eight folds after MT treatment, accompanied by the significant down-regulated expression of mutated ftsI and mrcA genes. Based on such results, we believed that MT could reverse the resistance of H. parasuis to CEC by inhibiting the mutations in ftsI and mrcA genes. Our research would provide useful information for restoring the antimicrobial activity of ß-lactams and improving the therapeutic efficacy of Glässer's disease.

Comparative study of the plasma pharmacokinetics and tissue residues of trimethoprim in silky fowls and 817 broilers after single oral administration.

A comparative study was performed to investigate the differences in plasma pharmacokinetics (PKs) and tissue residues of trimethoprim (TMP) between silky fowls and 817 broilers. The 2 breeds of chickens received compound sulfadiazine suspension by gavage at 20 mg/kg (measured as TMP). Blood and tissue samples were collected at predetermined time points. The concentrations of TMP in plasma and tissue samples were determined by a validated high-performance liquid chromatography (HPLC) method. The plasma concentration-time data were subjected to noncompartment analysis by WinNonlin program (Pharsight Co., Mountain View, CA). The mean plasma concentrations of TMP in silky fowls were significantly lower than those in 817 broilers at all time-points. Significant differences were also observed between silky fowls and 817 broilers in maximum concentration (Cmax), area under the curve from time 0 to 24 h (AUC0 â†’ 24 h), apparent volume of distribution (Vd), and total body clearance (ClB). Silky fowls had significantly higher muscle TMP concentrations and longer tissue residual time than 817 broilers. The tissue concentration of TMP followed the order of leg muscle > breast muscle > liver, which was obviously different from that of 817 broilers. The half-lives of TMP in the leg muscle, breast muscle, and liver of silky fowls were 31.42, 10.78, and 0.38 d, respectively. The current withdrawal time (WDT) was not sufficient to prevent violative residues of TMP in the edible tissues of silky fowls, and a WDT much longer than 8 d might be required.

A reliable, simple and cost-efficient TLC-HPLC method for simultaneously determining florfenicol and florfenicol amine in porcine urine: application to residue surveillance.

Violative residues of florfenicol (FF) in porcine edible tissues pose a potential risk for human health. In this study, urine was selected as target matrix for routine residue monitoring of FF in pig, and a thin layer chromatography (TLC)-high-performance liquid chromatography (HPLC) method was developed for simultaneously determining FF and florfenicol amine (FFA) in porcine urine. The urine samples were extracted with ethyl acetate under alkaline environment. The extracts were enriched through evaporation, purified by TLC and analysed by HPLC at 225 nm. A Waters Symmetry C18 column was used for the separation of the two analytes. The mobile phase was acetonitrile-phosphate buffer mixtures (33.3: 66.7, v/v), and was pumped at 0.6 mL/min. The TLC-HPLC method was well validated and successfully applied to residue depletion study. Good analytical specificity was confirmed by the lack of interfering peaks at the retention times of FF and FFA. The standard curves showed good linearity (FF: y = 143064x - 1045.3, r= 0.9999; FFA: y = 275826x + 1888.8, r= 0.9999) over the range of 0.0625-8 µg/mL. The precision ranged from 0.83% to 11.66% and 2.19% to 8.75% for intraday and interday determination, respectively. The corresponding accuracy ranged from -13.38% to 10.78% and -12.15% to 7.14%, respectively. The limits of quantification (LOQs) for FF and FFA were 0.125 µg/mL. The residue depletion study showed that the concentrations of FF and FFA in urine were higher than those in edible tissues at three time points. This method was reliable, simple and cost efficient, and could be used to monitor FF residues in porcine edible tissue without slaughtering animals. TLC showed excellent purification efficiency and is expected to solve matrix interferences in veterinary drug residue analysis.

Suboptimal chemotherapy is an adverse prognostic factor in osteosarcoma.

BACKGROUND: We sought to determine whether suboptimal chemotherapy compromised the prognosis of osteosarcoma patients. METHODS: A total of 132 eligible patients who underwent chemotherapy between 1998 and 2008 were identified in our database. Information regarding patient demographics, clinical characteristics, and survival status were extracted for analysis. Optimal chemotherapy was defined as receipt of ≥80% of the planned dose intensity of prescribed agents within the planned durations. RESULTS: The use of optimal chemotherapy resulted in an overall survival benefit with P = 0.006. Patients who failed to complete the optimal chemotherapy protocol had a dismal prognosis of 30.8% overall survival over five years, whereas those who completed the optimal chemotherapy had an overall survival rate over five years of 65.3%. Based on multivariate analysis, patients who were treated with a suboptimal protocol had a higher risk of relapse, metastasis and mortality. The hazard ratio (HR) of recurrence or death for the suboptimal chemotherapy group was as high as 2.512 over that of the optimal chemotherapy group (HR = 2.512, 95% confidence interval = 1.242 to 3.729). CONCLUSIONS: Chemotherapy is a significant independent prognostic variable, and suboptimal chemotherapy was found to have a detrimental effect on the outcome of patients with osteosarcoma.