There is a pressing need for new antibacterial agents due to the development of drug-resistant pathogens. Unfortunately drug development is a difficult and complicated process. The traditional approach in searching for a right dose is quite empirical, both costly and time-consuming. To enhance the ability to predict the likelihood of success for lead compound selection, in vitro pharmacodynamic and in vivo animal infection models are now extensively used. The value of these pre-clinical experiments, combined with mathematical modeling, helps to identify a pharmacokinetic (PK)-pharmacodynamic (PD) exposure measure which best predicts the therapeutic efficacy, and to quantify the magnitude of this index required for in vivo efficacy. PK-PD target attainment analyses using Monte Carlo simulation to integrate interpatient variability in drug exposure (PK), drug potency (MIC), and in vivo exposure targets that are predictive of positive therapeutic outcomes are influencing antibacterial drug development for proof of concept, for dose and dosing interval selection, for determining susceptibility breakpoints, and for evaluating the clinical meaning of antibacterial resistance. In this article, the key concepts of antibacterial PK-PD and model based antibacterial drug development strategy and process are critically reviewed.

Integration of pharmacokinetics(PK)/pharmacodynamics(PD)in antibiotic drug development allows the dosage regimen to be optimized,so that the desired effect can be achieved in a large proportion of the target patient population.In vitro kinetic and in vivo animal models have been extensively used in the evaluation of antibiotics.The value of these pre-clinical models in the PK and PD characterization of antibiotics is critically reviewed.A model based clinical development of antibiotics with integrating MIC distribution,PK parameter distribution,the PD target from animal models of infection,and the protein binding of the test drug,is also reviewed.

After birth,human intestinal tract mucosa is exposed to a large community of commensal and pathogenic bacteria. As a first line of defense,the intestinal epithelial barrier (IEB) kills the pathogen by signaling to the innate immune system, through pattern recognition receptors, while it produces protective respond towards the commensal bacteria. Intestinal epithelial cells play an important role in forming immune tolerance to the commensal bacteria and make intestinal homeostasis. Commensal bacteria can resist the pathogenic bacteria invasion. The signals of commensal are required for development of intestinal epithelial barrier and intestinal innate and adaptive immunity. It is essential for the host to have a balance between the commensal bacteria and intestinal tract,once the balance is broken, the intestinal inflammation disease will be caused. Thus ,this review will discuss the relationship between intestinal commensal bacteria and intestinal epithelial barrier in several aspects, such as the role of the commensal bacteria, the mechanism of producing commensal tolerance by IEB and the disease caused by imbalance between the commensal and IEB.

Humans ; Skin ; pathology ; Trichloroethylene ; poisoning

Humans ; Male ; Middle Aged ; Occupational Diseases ; complications ; Pulmonary Edema ; chemically induced ; Trimethylsilyl Compounds ; poisoning

Acute Disease ; Humans ; Male ; Middle Aged ; Occupational Diseases ; diagnosis ; therapy ; Phosgene ; poisoning ; Poisoning ; diagnosis ; therapy

China ; Health Promotion ; methods ; Health Status ; Humans ; Nutritional Status ; Social Class ; Socioeconomic Factors

[Objective]To investigate the effective method for allergic rhinitis.[Method]58 cases were randomly divided into 2 groups,treatment group 31 take self-made Yiqi Tuomin Decoction,other group 27 take cetirizine hydrochloride.[Result]In treatment group,16 cases had marked effect,12 had effect,3 had no effect,effective rate was 90.3%;for control one,they were 8,10,9 and 66.7%respectively.[Conclusion]Yiqi Tuomin Decoction has obvious effect on allergic rhinitis.

Objective To evaluate the effects of application of MgCI2, ATP, and ATP-MgCl2 on the funcrions of liver, kidney, heart and lung in experimontelly ischemic injuried animals, and to study the therapeutic role of exogenous Mg2+ and energy on repairmat of this injuny ming. Freeze etching, Histochemistry, Atomic Absorhtion Spectrum (AAS) and combine LM and EM. The experiment showed that MgCl2 and ATP protectived functions damnify organic (P>0.01) ,ATP-MgCl2 protected effect it notable results (P<0.01 ). Cell membrance was complete, glycogen became enriched in the cytoplasm, the uniform-distributed protein granule on Pside of plasma membtance of cell was found. There were positive material in the membrances and similar to normal group, cell michondia calcium decreased. Conclusions The exogenous application of ATP-MgCl was beneficial to the critical patient.

Objective To observe and evaluate the clinical effects of thymosin ?1 on gastrointestinal carcinoma in elderly patients.Methods Ninety-six aged patients with gastrointestinal carcinoma in the General Hospital of PLA,who had received chemotherapy,were randomly divided into two groups(n=48 for each group): control group and treatment group.Patients in the treatment group received thymosin ?1 by subcutaneous injection in a dose of 1.6mg,the treatment was given once every other day and the whole course lasted for 8 weeks;while patients in the control group received physiological saline solution in the same amount only instead of thymosin.For the patients in both groups,the activities of peripheral blood T cell subsets,such as CD4+,CD4+/CD8+ and natural killer(NK),were measured by flow cytometry before the treatment and in the 2nd,4th,8th week of chemotherapy.The life quality of every patient was evaluated by Karnofsky scores at the same time.Results After the treatment,the Karnofsky scores in the treatment group were much higher than that in the control group(P