ABSTRACT
The shortage of effective antibiotics against multidrug-resistant Acinetobacter baumannii [MDR-Ab] has posed great threat to the public health. But the advent of tigecycline gives us new hope. The goal of our research was to assess the clinical efficacy of tigecycline at different doses by using a pharmacokinetic/pharmacodynamic [PK/PD] model which can incorporate pharmacokinetic data of tigecycline from patients with pneumonia and MICs of MDR-Ab from a tertiary hospital. A 10000-patient Monte-Carlo Simulation based on the PK/PD model was conducted to calculate the probability of target attainment [PTA] and the cumulative fraction of response [CFR] of tigecycline. 97% isolates displayed susceptibility and 3% were tigecycline-intermediate strains and the values of MIC ranged from 0.125 to 4microg/ml. A CFR of 61.62% was predicted for tigecycline at current dosage [50 mg q12h]. When the dosage was increased, the predicted CFRs for 75 mg q12h, 100 mg q12h, 125 mg q12h, 150 mg q12h were 81.00%, 89.86%, and 94.57%, 96.77%, respectively. Despite presented higher susceptibility, the CFR obtained was not optimal at current dosage. A higher CFR indicating a better clinical efficacy can be gained by the increased dosage.
Subject(s)
Humans , Pneumonia/drug therapy , Cross Infection , Drug Resistance, Multiple , Acinetobacter baumannii , Minocycline/pharmacologyABSTRACT
Objective To study the effects of apoptosis-stimulating protein of ρ53-2 (ASPP2) gene on hepatocellular carcinoma (HCC) cell proliferation and apoptosis under starvation and the related mechanism. Methods Lentivirus encoding shRNA against ASPP2 was constructedto knockdown ASPP2 expression in hepatoma cell HepG2. Cell proliferation and apoptosis were observed by transmission electron microscopy, MTS analysis, flow cytometry analysis and morphologic changes. The influence of silencing ASPP2 gene on the proliferation and apoptosis under amino acid-starvation and serum-deprivation culture was observed; autophagy inhibitor 3-methyladenine (3-MA) was added in the experiment so as to detect the involvement of autophagy in the changes induced by ASPP2 down-regulation. Results Transmission electron microscopy showed cytoplasmic accumulation of autophagosomes when ASPP2 was knocked down under amino acid-starvation and serum- deprivation (P<0. 05), with increased GFP-LC3 dots (P<0. 05). MTS analysis showed that silence of ASPP2 gene greatly enhanced the proliferation of HepG2 cells (P<0. 05), which could be inhibited by addition of 3-MA (P<0. 05). Microscope observation showed that silence of ASPP2 gene promoted the anti-apoptotic ability of HepG2 cells, which was reversed by treatment with 3-MA. Early sign of apoptosis was observed in shASPP2 + 3-MA group. Annexin V_PI double staining showed that ASPP2 silence decreased the apoptotic rate ofHepG2 cells from (38±5)% to(15±4)% (P<0. 05), and 3-MA treatment increased it to (36 ±3)% (P<0. 05). Conclusion Down-regulation of ASPP2 expression may facilitate the survival and proliferation of HCC cells through activating autophagy under starvation.
ABSTRACT
Influence of iron-depletion on twitching motility and quorum sensing (QS) system in P. aeruginosa was evaluated. The results demonstrated iron-depletion can retard biofilm formation and increase the twitching motility and expression of QS-related genes, suggesting a potential interaction between twitching motility and QS system in P. aeruginosa biofilm formation.