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 ; 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

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.

Background and purpose:HIF-1? (Hypoxia-inducible factor-1?) is an important transcription factor under hypoxia condition. It plays the role of dominating the expressions of correlative genes. It also promotes tumor deterioration, tumor metastasis and tumor invasion. The molecular role of HIF-1? has been intensively studied in cancer basic research. This article is to investigate the expression of HIF-1? under hypoxic and reoxygenation induced by CoCl_ 2 and the impact of hypoxia-inducible transcription factor-1? on human ovarian carcinoma cell line HO-8910PM. Methods:Semi quantitative reverse transcription-polymerase chain reaction (RT-PCR) is performed to detect the expression of HIF-1? mRNA in human ovarian carcinoma cell HO-8910PM exposed during the phase of hypoxia and reoxygenation. The relations of the quantity-efficiency and the time-efficiency were analyzed. The effects of HIF-1? gene on the proliferation, invasion and adhesion of HO-8910PM cell were estimated by either MTT, Boyden cell or cell adhesion tests.Results:There was endogenous expression of HIF-1? in human ovarian carcinoma cell line HO-8910PM. RT-PCR show that over-expression of HIF-1? mRNA could be measured under hypoxia induced by CoCl_ 2 (P

OBJECTIVE: To assess the efficacy and safety of Sanjin tablets in the treatment of urinary tract infection. METHODS: Retrieved from electronic databases and references literatures by on-line or manual way, RCTs about Sanjin tablets in the treatment of urinary tract infection were collected. Related data were obtained and analyzed with evidence-based medical software statistically. RESULTS: 1 046 patients in 13 studies with were included. Two studies showed that Sanjin tablets had better effect than amoxicillin, ciprofloxacin, erythromycin and norfloxacin in the treatment of urinary tract infections. One study showed there was no significant difference in efficacy of Sanjin tablets and Modified juling tang. Other trials showed that there was no difference in efficacy between Sanjin tablets and Chinese herbal medicine, antibiotics. Three trials showed Sanjin tablets combined with Chinese herbal medicine or antibiotics had the same effect with antibiotics alone in the treatment of urinary tract infection. No severe ADR induced by Sanjin tablets was found in included studies. Funnel plot which assumed asymmetry indicated the existence of publication bias and unsatisfactory methodological quality. CONCLUSION: Few trials show efficacy of Sanjin tablets are better than antibiotics. Most of studies show that there is no significant difference between Sanjin tablets and antibiotics. At present no evidence indicate that efficacy of Sanjin tablet is superior to other drugs. The methodological quality of clinical trials of Sanjin tablets for urinary tract infections should be improved.

Animals ; Fatty Liver ; complications ; genetics ; metabolism ; virology ; Hepatitis B virus ; genetics ; isolation & purification ; physiology ; Hepatitis C, Chronic ; complications ; genetics ; metabolism ; virology ; Humans

Abstract: Based on years of ancient literature research and clinical experience, Professor Pin-kang Wei developed the phlegm theory of gastric cancer. In light of the properties of gastric cancer and the method of differentiating syndromes within the traditional Chinese medicine (TCM) paradigm, it is believed that gastric cancer is closely related with phlegm. Much ancient literature regarding the relationship between phlegm and gastric cancer was reviewed to explain the rationale and academic inheritance of the phlegm theory. In this theory, gastric cancer is regarded as a form of phlegm stagnation and consists of phlegm core, phlegm collateral and phlegm contamination. In order to explain the mechanism of development, recurrence and metastasis of gastric cancer, phlegm contamination is regarded as the most fundamental cause and pathogenesis of gastric cancer. The therapy of resolving phlegm and dispersing nodules is suggested for the fundamental treatment of gastric cancer.