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.

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

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

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

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.

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

China ; Food Safety ; Risk Assessment

Objective To summarize the herbal medication in treating malignant ascites based on literature. Methods TCM literatures concerning malignant ascites from CNKI (1989.1-2013.3) were retrieved. The herbs and those category, nature, flavor and meridian distribution were summarized by frequency method. The couple herbs were analyzed by hierarchical cluster analysis. Results Fifty-five qualified documents and 56 effective prescriptions were collected. A total of 164 herbs were used (668 frequencies). Six groups of herbs, cumulative relative frequency (CRF) of 61.83%, were used frequently in order as follows:the herbs for promoting diuresis and resolving dampness, invigorating qi, invigorating the blood and removing blood stasis, regulating qi, eliminating heat and toxin, excreting drastically water. The most frequently used herbs (>6 frequencies, CRF 53.74%) had 25 species. The first three places were the herbs for promoting diuresis and resolving dampness (5 species), invigorating qi (4 species), invigorating the blood and removing blood stasis (3 species). These herbs were mostly of warm nature (260 frequencies, 38.92%). The total frequency of herb-nature was 1055 and the sweet (354 frequencies, 33.55%), bitter (284 frequencies, 26.92%) and pungent (268 frequencies, 25.40%) herbs were used more frequently. The total frequency of meridian distribution was 1747 and these herbs were mostly attributed to spleen, lung, liver, and kidney meridians (>200 frequencies). The most frequently used couple-herbs included Poria and Rhizoma Atractylodis Macrocephalae, Radix Astragali and Ramulus Cinnamomi, etc. Conclusion Invigorating qi was emphasized in treating malignant ascites, combined with promoting diuresis. The herbs of the warm and cold nature, the sweet, bitter and pungent flavor, spleen, lung, liver and kidney meridians were most frequently used.

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.