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.

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

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.

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

The Weibel-Palade-like body were found in the cytoplasm of the growth hormone and follicullar - stellate cells of rabbit adenopypophsis. The body is surrounded by a single unit membrane. In this body, there are numerous of microtubules which can be divided into two groups depending upon their diameters.Yet, it is uncertain what the virtual function is and where the bodies come from. However, according to the experimental observations, it is suggested that the body serve as a mechanical power device which has relations with the regional distribution of the organelles. The intranuclear microtubules and intranuclear tubules were also found in the growth hormone cells. The diameters of these intranuclear microtubules range from 25 - 30 nm, and the intranuclear tubule about 78 nm. The fomer seems to be connected with the heterochromatin granules, and may be. a transitional pattern from heterochromatin to euchromatin, but their importance remain to be clarified.

The ultrastructural changes in growth hormone (GH) cells of rabbit adeno-hypophysis are determined quantitatively with stereological method after burn injury. Blood sugar levels are concurrently measured. The results show: the volume fraction of Golgi complex, mitochondria and rough endoplasmic reticulum shows a 2-phase curve after burn, and it may be divided into 3-periods stress, modulation and functional activation and recovery; the rate of maturation of secretory granules is increased; a close relation between the blood sugar and some activities of GH cell secretion after burn presents; the autocrine shows a negative feedback to the exocytosis in the control group,and a positive feedback in burned ones; the newly formed mitochondria may be originated from the new Golgi complex from the reutilization of plasma components.