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

Humans ; Skin ; pathology ; Trichloroethylene ; poisoning

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

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.

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

China ; Food Safety ; Risk Assessment

Child ; Child, Preschool ; China ; epidemiology ; Food Contamination ; Humans ; Infant ; Infant Formula ; chemistry ; Infant, Newborn ; Triazines ; poisoning ; Urinary Calculi ; chemically induced ; epidemiology

Extramedullary infiltration is one of the reasons of relapse and death for leukemia patients.Reaearches increasingly show that extramedullary microenvironment plays a pivotal role on progress and relapse of leukemia.Extramedullary infiltration of leukemia is the result of interactions among many factors and many steps,involving liver,spleen,central nervous system,thymus and other tissues and organs.