64 research outputs found
Ethanolic Allium sativum extract down-regulates the pelF gene involved in Pseudomonas aeruginosa biofilm formation
No full textExploration of efficacious plant extracts that can reduce or inhibit Pseudomonas aeruginosa biofilm formation is necessary. Allium sativum is a suitable candidate because of its relative abundance. This study was carried out to determine the effect of ethanolic A. sativum extract on the expression of the P.aeruginosa biofilm gene, pelF. The presence of the pelF gene in the isolates used for this study was confirmed via polymerase chain reaction (PCR) and agarose gel electrophoresis. P. aeruginosa culturestreated with 1 g/ml of the A. sativum extract had the least turbidity (6.7 absorbance value at A600). The expression profile of the pelF gene in the treated cultures was determined via PCR using cDNA synthesized from RNA isolated from the treated P. aeruginosa cultures. The amplicons from the PCR were analyzed via agarose gel electrophoresis and a concentration dependent down-regulation of the pelF gene was observed. Further quantification of the pelF gene’s expression was performed via realtime PCR using rpoB as the reference gene. A 4-fold down-regulation of the gene was observed at 0.5and 1 g/ml concentrations, respectively. This study suggests that the suppression of the pelF gene of P. aeruginosa by A. sativum extracts plays a role in the inhibition of P. aeruginosa biofilm formation. This is the first study to elucidate the effect of A. sativum on the expression of any of the pel genes
Exploration of Clinical Breakpoint of Danofloxacin for <i>Glaesserella parasuis</i> in Plasma and in PELF
No full textBackground: In order to establish the clinical breakpoint (CBP) of danofloxacin against G. parasuis, three cutoff values, including epidemiological cutoff value (ECV), pharmacokinetic-pharmacodynamic (PK-PD) cutoff value (COPD) and clinical cutoff value (COCL), were obtained in the present study. Methods: The ECV was calculated using ECOFFinder base on the MIC distribution of danfloxacin against 347 G. parasuis collected from disease pigs. The COPD was established based on in vivo and ex vivo PK-PD modeling of danofloxacin both in plasma and pulmonary epithelial lining fluid (PELF) using Hill formula and Monte Carlo analysis. The COCL was established based on the relationship between the possibility of cure (POC) and MIC in the clinical trials using the “WindoW” approach, nonlinear regression and CART analysis. Results: The MIC50 and MIC90 of danofloxacin against 347 G. parasuis were 2 μg/mL and 8 μg/mL, respectively. The ECV value was set to 8 μg/mL using ECOFFinder. Concentration-time curves of danofloxacin were fitted with a two-compartment PK model. The PK parameters of the maximum concentration (Cmax) and area under concentration-time curves (AUC) in PELF were 3.67 ± 0.25 μg/mL and 24.28 ± 2.70 h·μg/mL, higher than those in plasma (0.67 ± 0.01 μg/mL and 4.47 ± 0.51 h·μg/mL). The peak time (Tmax) in plasma was 0.23 ± 0.07 h, shorter than that in PELF (1.61 ± 0.15 h). The COPD in plasma and PELF were 0.125 μg/mL and 0.5 μg/mL, respectively. The COCL calculated by WindoW approach, nonlinear regression and CART analysis were 0.125–4 μg/mL, 0.428 μg/mL and 0.56 μg/mL, respectively. The 0.5 μg/mL was selected as eligible COCL. The ECV is much higher than the COPD and COCL, and the clinical breakpoint based on data in plasma was largely different from that of PELF. Conclusions: Our study firstly established three cutoff values of danofloxacin against G. parasuis. It suggested that non-wild-type danofloxacin-resistant G. parasuis may lead to ineffective treatment by danofloxacin
A phase II study of sequential chemotherapy with docetaxel after the weekly PELF regimen in advanced gastric cancer. A report from the Italian group for the study of digestive tract cancer.
No full textIn advanced gastric cancer, we investigated feasibility and activity of sequential chemotherapy with docetaxel after an intensive weekly regimen consisting of cisplatin, epidoxorubicin, fluorouracil, leucovorin (PELF) plus filgrastim. Chemotherapy-naive patients with relapsed or metastatic gastric cancer received 8 weekly administrations of chemotherapy with cisplatin 40 mg/m(2), fluorouracil 500 mg/m(2), epidoxorubicin 35 mg/m(2), 6S-stereoisomer of leucovorin 250 mg/m(2) and glutathione 1.5 g/m(2). On the other days filgrastim 5 microg kg(-1) was administered by subcutaneous injection. Subsequently, patients with partial response or stable disease received 3 cycles of docetaxel 100 mg/m(2) every 3 weeks. 40 patients have been enrolled and they are evaluable for response and toxicity. After the PELF regimen, 3 patients achieved complete response, 13 patients showed partial response, 21 patients had stable disease and 3 patients progressed (40\% response rate; 95\% CI 25\% to 55\%). After docetaxel, 9 out 34 patients improved the outcome (26.5\%); 7 patients with stable disease achieved partial response and 2 patients with partial response achieved complete response. The overall response rate in the 40 patients was 57.5\% (95\% CI, 42.5\% to 72.5\%). The PELF regimen did not cause any grade IV toxicity, the most frequent grade III acute side-effects were thrombocytopenia and vomiting which occurred in the 10\% of 320 PELF cycles. Docetaxel caused grade III-IV neutropenia and thrombocytopenia in the 10\% and the 19\% of cycles respectively. Fatigue was a frequent side-effect during both PELF and docetaxel chemotherapy. The sequential application of docetaxel after PELF chemotherapy gained major objective responses with manageable toxicity. This strategy is worth of further investigation in the setting of palliative or neoadjuvant chemotherapy
Pulmonary Epithelial Lining Fluid (PELF) Pharmacokinetics of Enrofloxacin and Ciprofloxacin after Administration of 7.5 mg/kg of Enrofloxacin to Calves.
No full textPulmonary Epithelial Lining Fluid (PELF) Pharmacokinetics of Enrofloxacin and Ciprofloxacin after Administration of 7.5 mg/kg of Enrofloxacin to Calves.</p
Fluorouracil, doxorubicin, and mitomycin combination versus PELF chemotherapy in advanced gastric cancer: a prospective randomized trial of the Italian Oncology Group for Clinical Research.
No full textPURPOSE The combination of cisplatin, epirubicin, and leucovorin preceding fluorouracil (PELF) includes three novel agents compared with the standard combination of fluorouracil, doxorubicin, and mitomycin (FAM) in the treatment of advanced gastric carcinoma. We report the results of a prospective randomized comparison of the two combinations in previously untreated patients. PATIENTS AND METHODS One hundred thirty assessable patients were entered onto the trial; 52 received FAM and 85 PELF. A 1:2 unbalanced randomization in favor of the experimental treatment was chosen. Approximately 90% of patients had measurable tumor masses. RESULTS The overall response rates (complete responses [CRs] and partial responses [PRs]) were 15% and 43% for the FAM and the PELF regimens, respectively, with a statistically significant advantage for the experimental treatment (P = .001). Time to progression (median, 2.6 and 4.7 months), duration of response (median, 10.7 and 10.2 months), and survival durations (median, 5.6 and 8.1 months) were not significantly different between the FAM and PELF regimens, respectively. The PELF combination was more toxic compared with FAM, but generally tolerable. CONCLUSION This study showed that the PELF combination is about three times more effective than the FAM combination in inducing objective responses. Due to tolerability, it is not recommended for routine clinical use. However, it should be considered, among other second-generation chemotherapy combinations, in future randomized studies aimed to improve the therapeutic outcome in gastric carcinoma. </jats:sec
Plasma, Insterstitial Fluid (ISF), and Pulmonary Epithelial Lining Fluid (PELF) Pharmacokinetics after Administration of 2.5 mg/kg of Tulathromycin to Calves.
No full textPlasma, Insterstitial Fluid (ISF), and Pulmonary Epithelial Lining Fluid (PELF) Pharmacokinetics after Administration of 2.5 mg/kg of Tulathromycin to Calves.</p
Plasma, Insterstitial Fluid (ISF), and Pulmonary Epithelial Lining Fluid (PELF) Pharmacokinetics after Administration of 40 mg/kg of Florfenicol to calves.
No full textPlasma, Insterstitial Fluid (ISF), and Pulmonary Epithelial Lining Fluid (PELF) Pharmacokinetics after Administration of 40 mg/kg of Florfenicol to calves.</p
Plasma, Insterstitial Fluid (ISF), and Pulmonary Epithelial Lining Fluid (PELF) Pharmacokinetics of Ceftiofur and Ceftiofur Derivatives after Administration of 6.6 mg/kg of Ceftiofur Crystalline Free Acid to calves.
No full textPlasma, Insterstitial Fluid (ISF), and Pulmonary Epithelial Lining Fluid (PELF) Pharmacokinetics of Ceftiofur and Ceftiofur Derivatives after Administration of 6.6 mg/kg of Ceftiofur Crystalline Free Acid to calves.</p
Pharmacokinetics of florfenicol in turkey plasma, lung tissue, and pulmonary epithelial lining fluid after single oral bolus or continuous administration in the drinking water
No full textFlorfenicol (FF) is registered for treatment of bovine and swine respiratory diseases. Although, turkeys often suffer from bacterial respiratory tract infections, there is no registered formulation based on FF for poultry available in Europe. The aim of this study was to evaluate the pharmacokinetic behavior of FF in turkeys in plasma, lung tissue, and pulmonary epithelial lining fluid (PELF).
The concentration and pharmacokinetic characteristics of FF in plasma, lung tissue, and PELF in turkeys were determined, either after a single oral bolus (30 mg/kg body weight, BW) or during and after continuous drinking water medication (30 mg/kg BW/d for 5 d). Plasma, lung tissue, and PELF samples were collected at different intervals after administration, and FF was quantified by liquid chromatographytandem mass spectrometry. After single bolus administration, FF was rapidly absorbed in plasma (the time to maximum concentration, t(max), was 1.02 h) and distributed to the respiratory tract (mean t(max) = 1.00 h). The mean t(1/2el) in plasma and lung tissue was similar, around 6 h, whereas it was slightly higher in PELF, namely, 8.7 hours. After oral bolus dosing, the mean maximum concentration in plasma was twice as high as in the lung tissue, 4.26 mu g/mL and 2.64 mu g/g, respectively, while in PELF it was much lower, 0.39 mu g/mL. During continuous drinking water medication, lung FF concentrations were slightly higher than plasma concentrations, with lung/plasma ratios of 2.01 and 1.27 after 24 h and 72 h, respectively. FF was not detected in PELF during continuous drinking water medication
Bronchopulmonary pharmacokinetics of (R)- salbutamol and (S)-salbutamol enantiomers in pulmonary epithelial lining fluid and lung tissue of horses
No full textAims: Salbutamol is usually administered as a racemic mixture but little is known about the enantioselectivity of salbutamol pharmacokinetics in the lung. This study was designed to investigate enantiomer concentrations in lung tissue after inhaled dosing. Methods: Horses (n = 12) received racemic salbutamol 1000 μg via inhalation. Enantioselective ultra performance liquid chromatography–tandem mass spectrometry was used to determine salbutamol concentrations in pulmonary epithelial lining fluid (PELF) sampled 2, 5, 10 and 15 min after administration, in central lung (endoscopic bronchial biopsy) and peripheral lung (percutaneous pulmonary biopsy) tissues (at 20 and 25 min respectively), and in plasma samples. Results: Mean ± 95% confidence interval (CI) yield of PELF was 57 ± 10 mg. Initial mean ± 95%CI (R)- and (S)-salbutamol PELF concentrations were 389 ± 189 ng g–1 and 378 ± 177 ng g–1 respectively, and both reduced approximately 50% by 15 min. Mean ± 95%CI central lung levels of drug were higher than peripheral lung tissue for both (R)-salbutamol (875 ± 945 vs. 49.5 ± 12 ng g–1) and (S)-salbutamol (877 ± 955 vs. 50.9 ± 12 ng g–1) respectively. There was no evidence of enantioselectivity in PELF or central lung but minor (~2%) enantioselectivity was observed in the peripheral lung. Enantioselectivity was clearly evident in plasma with (S):(R) ratio of 1.25 and 1.14 for both area under the concentration–time curve (0–25 min) and Cmax respectively. Conclusion: PELF sampling in horses offers sufficient yield allowing direct detection of drug and, combined with tissue sampling, is a valuable model to investigate bronchopulmonary pharmacokinetics. Salbutamol did not demonstrate enantioselectivity in PELF or central lung tissue uptake following acute dosing, however, enantioselective plasma concentrations were demonstrated, with minor enantioselectivity in the peripheral lung.</p
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