Multidrug-resistant (MDR) bacterial infections, especially those caused by Gram-negative pathogens, have emerged to be one of the world's greatest health threats. However, not only have recent decades shown a steady decline in the number of approved antimicrobial agents but a disappointing discovery also void. The development of novel antibiotics to treat MDR Gram-negative bacteria has been stagnated over the last half century. Though few compounds have shown activities in vitro, in animal models or even in clinical studies, the global antibiotic pipeline is not encouraging. There are a plethora of unexpected challenges that may arise and cannot always be solved to cause promising drugs to fail. This review intends to summarize recent research and development activities to meet the inevitable challenge in restricting the proliferation of MDR Gram-negative bacteria, with focus on compounds that have entered into clinical development stage. In addition to new analogues of existing antibiotic molecules, attention is also directed to alternative strategies to develop antibacterial agents with novel mechanisms of action.
Aminoglycosides ; pharmacology ; therapeutic use ; Animals ; Anti-Bacterial Agents ; pharmacology ; therapeutic use ; Antibodies, Monoclonal ; pharmacology ; therapeutic use ; Drug Discovery ; Drug Resistance, Multiple, Bacterial ; Enzyme Inhibitors ; pharmacology ; therapeutic use ; Ferrous Compounds ; pharmacology ; therapeutic use ; Gram-Negative Bacteria ; drug effects ; Gram-Negative Bacterial Infections ; drug therapy ; Humans ; Peptides ; pharmacology ; therapeutic use ; Peptidomimetics ; pharmacology ; therapeutic use ; Tetracyclines ; pharmacology ; therapeutic use ; beta-Lactamase Inhibitors ; beta-Lactams ; pharmacology ; therapeutic use

0.05). Conclusion Tianma Gouteng Decoction can reverse left ventricular hypertrophy and myocardial fibrosis,and its mechanism may be related to the inhibition of TGF-? 1 expression in cardiac muscle tissue.

The high production inulase strain was screened from the soil sample where burdock planted in Qin Village,Bayou Town,Pei County,Xuzhou.Inulase activity were determined which produced by 40 strains separated from soil.Three mold stains,C122803、D081506 and D081513,which had higher ability of producing inulase were obtained by using transparent circle method as initial screening and rocker method as re-screening.Enzyme activity of the three strains were 1.411U/ml,1.895U/ml,1.792U/ml,separately.Enzyme activity of D081506,1.895U/ml,was the highest.The fermentation conditions of D081506 were studied and the optimized conditions were lappa juice 2.0%,yeast extraction 1.6%,(NH4)2SO4 0.5%,NaCl 0.5%,K2HPO4 0.5% and pH 5.0.Inulase activity of D081506 was 2.9578U/ml which increased 56.09% under the condition of 27℃,140r/min,24h.

Osteoarthritis (Osteoarthritis, OA) is a common clinical degenerative joint disease with increased incidence rate in recent years. Animal experiment is one of the important ways to explore pathogenesis and treatment of OA, while induced animal model is the most important part in animal experiment. Intra-articular injection of drugs is a classical method for establishing animal model of OA. Choose of animal should follows the principle of correlation, appropriateness and practicability, injections should perform in accordance with experimental purposes and subject, detections means and evaluation methods also should corresponding to experimental reality. The gold standard of OA animal model and intra-articular injections has not build, need further study.
Animals ; Cytokines ; analysis ; Disease Models, Animal ; Injections, Intra-Articular ; Mice ; Osteoarthritis ; diagnosis ; etiology ; immunology ; Rabbits ; Rats

Objective To observe the effect of small doses of thrombin inhibitor(Shuxuetong injection)on the absorption of hematoma and the volume of low-density areas in acute stage of cerebral hemorrhage.Methods One hundred and twenty patients with acute cerebral hemorrhage,admitted to our hospital from February 2004 to April 2009,were randomly divided into treatment and control groups (n=60).The treatment group was treated with routine western medicine combined with thrombin inhibitor (Shuxuetong injection)4 mL dairy intravenously for 15 consecutive d.CT scan was employed to evaluate the hematomas volume and changes of low-density areas 7 and 21 d after the treatment.Results The volume of hematomas in the treatment group(17.8±2.1 mL,8.2±2.1 mL)reduced significantly as compared with that in the control group(21.3±1.6 mL,15.1±1.2 mL)on the 7~(th) and 21~(st) d(P<0.05).The volume of low-density area in the treatment group(1.433 mm)was significantly reduced as compared with that in the control group(3.041 mm,P<0.05).Conclusion Small doses of thrombin inhibitor (Shuxuetong injection)can promote the absorption of hematoma,reduce the volume of low-density areas surrounding hematomas in acute stage of cerebral hemorrhage.

OBJECTIVEChina began providing antiretroviral therapy to people living with HIV/AIDS (PLWHA) in 2003. This study was to investigate the living conditions, including quality of life and happiness, and need for palliative care of end-of-life PLWHA in rural Henan.

METHODSOne hundred end-of-life AIDS patients were selected from Weishi, Zhenping and Tanghe counties in Henan, using convenience sampling. The World Health Organization Quality of Life for HIV (WHOQOL-HIV) BREF Chinese Version was used to measure the quality of life and the Memorial University of Newfoundland Scale of Happiness (MUNSH) was employed to measure subjective welfare. Qualitative interviews and focus group discussions were undertaken to learn about the palliative care provided and the specific needs of the end-of-life patients.

RESULTSPatients' overall quality of life was moderate (12.62±1.97). Highest scores were in the spirituality/religion/personal beliefs, higher than the average scores in the Chinese population (P<0.01), while psychological (13.58±2.06) and environment (12.50±3.28) domain scores were similar to the latter (P>0.05). Both independence (12.15±2.15) and physiological (14.04±3.16) domain scores were lower than the average of the people living with HIV/AIDS in other studies (P<0.01); however, all were in the moderate range. The average MUNSH score was 21.00±6.20, which was also moderate. The in-depth interviews indicated that the Henan Provincial Government's policy of treatment and care had a beneficial impact on end-of-life AIDS patients, although the care components could be improved.

CONCLUSIONSLiving conditions of the end-of-life AIDS patients were moderate, and the HIV/AIDS palliative care model used was beneficial to them. Care could be improved by assisting the family unit as a whole.

Acquired Immunodeficiency Syndrome ; drug therapy ; epidemiology ; psychology ; therapy ; Adult ; Antiretroviral Therapy, Highly Active ; Blood Donors ; psychology ; China ; Critical Illness ; Female ; HIV Infections ; drug therapy ; epidemiology ; psychology ; therapy ; Humans ; Male ; Palliative Care ; standards ; Plasma Exchange ; statistics & numerical data ; Quality of Health Care ; Quality of Life ; Rural Population ; Surveys and Questionnaires

OBJECTIVE To explore the neuro-protective effects of saffron (Crocus satius L.) on chronic focal cerebral ischemia in rats.METHODS SD rats were randomly divided into 6 groups:sham control group,MCAO group,edaravone group and saffron 30,100,300 mg·kg-1groups.Focal cerebral ischemia was induced by middle cerebral artery occlusion(MCAO).Saffron was administered orally by once daily from 2 h to 42 d after ischemia. At 42 d after cerebral ischemia, neurological deficit score, spontaneous activity test,elevated plus maze test,marble burying test and novel objective recognition test were used to evaluate the effects of saffron on the behevioural change. Infarct volume, survival neuron density, activated astrocyte number, and the thickness of glial scar were also detected. GFAP expression and inflammatory cytokine contents in ischemic peripheral region were detected by Western blot and ELISA,separately.RESULTS Saffron(100,300 mg·kg-1)improved the body weight decrease, neurological deficit and spontaneous activity. Saffron (30-300 mg·kg- 1) increased the traveled distance ratio and total time in open arm, decreased the buried marble number, which indicated that saffron could ameliorate anxiety- and depression-like behaviors. Saffron (100, 300 mg·kg-1)improved the learning and memory function,which manifested by increased discrimination ratio(DR)and discrim-ination index (DI) in T2test. The results of toluidine blue found saffron treatment (100, 300 mg·kg-1) decreased the infarct volume and increased the neuron density in cortex and hippocampal.The activated astrocyte number,the thickness of glial scar and GFAP expression in ischemic peripheral region decreased after saffron. Saffron (100, 300 mg·kg-1) decreased the contents of IL-6 and IL-1β, increased the content of IL-10 in ischemic peripheral region.CONCLUSION Saffron exerted neuro-protective effects on chronic focal cerebral ischemia,which could be related with inhibiting the activation of astrocyte and glial scar,following with the decrease of inflammatory reaction.

OBJECTIVETo investigate the effect of sulindac on proliferation and apoptosis of human gastric cancer BGC-823 cells and its antineoplastic mechanisms.

METHODSHuman gastric cancer BGC-823 cells were incubated with sulindac at various concentrations and for different times. Morphological changes of BGC-823 cells were observed under an inversion microscope. MTT colorimetric assay was used to examine the effect of sulindac on the proliferation of BGC-823 cells. Flow cytometry was used to determine the cell cycle distribution and apoptosis. Transmission electron microscopy was performed to examine cell apoptosis morphology. Immunohistochemical staining was used to detect the expressions of COX-2, bcl-2 and ki-67 in the cells.

RESULTSsulindac induced morphologic alterations in BGC-823 cells, inhibited cell proliferation, increased the proportion of cells in G0/G1 phase and decreased the proportion of cells in S phase, induced apoptosis of BGC-823 cells, and decreased expressions of COX-2, bcl-2, ki-67 in the cells. All the effects were in a time- and dose-dependent manner (P < 0.05). Some characteristic morphologic features of apoptosis were revealed by transmission electron microscopy.

CONCLUSIONsulindac may inhibit the growth of gastric cancer BGC-823 cells in vitro and the anti-tumor mechanism may be related to changes in cell cycle distribution, induction of apoptosis and inhibition of expression of COX-2, bcl-2, and ki-67.

Antineoplastic Agents ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclooxygenase 2 ; metabolism ; Dose-Response Relationship, Drug ; Humans ; Ki-67 Antigen ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; Sulindac ; administration & dosage ; pharmacology

Promoting the construction of healthy enterprises in the China's coal industry will help coal enterprises to fulfill their ， ， legal and social responsibilities contribute to the construction of healthy cities and protect the health of occupational ， ， individuals from various aspects. In recent years the patriotic health campaign the health promotion project of industrial and ， ， ， mining enterprises the construction of standardized management system of coal mine safety the construction of green mines and the construction project of staff quality have laid the foundation for the construction of healthy enterprises in China's coal ， industry. However the development of coal industry in China is unbalanced and insufficient. There are many problems such as a ， general lack of professional talents the exist of a large number of small coal mines and the underprivileged technology of coal ， ， ， mining poor working environment in underground coal mines many occupational hazards in workplace and relatively few special incentive measures for the construction of healthy enterprises in the coal industry. It is recommended that coal ， enterprises with advanced productivity take the lead to demonstrate coal mine industry construction actively promote advanced ， ， and applicable technology and equipment steadily improve the professional level of coal industry workers comprehensively ， ， improve the environment of mining areas strengthen the monitoring and treatment of occupational hazards improve and ， - implement special incentive measures for healthy enterprises and comprehensively promote the high quality development of coal industry and the construction of healthy enterprises. So as to effectively protect the health occupational rights and interests of workers and provide assistance for occupational health work in the new era.

OBJECTIVE: To explore the inhibitive effects of 1,3,8-trihydroxy-5-methoxyxanthone (TMX) on cytochrome P450s (CYP450s) in human liver microsomes. METHODS: Probe drugs were incubated with and without adding TMX to determine the changes of enzyme activities. The concentration ratio of metabolites to probe drugs was used to present enzyme activities. Concentrations of the probe drugs and their metabolites in the incubated mixture were detected by high performance liquid chromatography. RESULTS: The variations (mean, 95%CI) of the activities of CYP1A2, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 were 2.95 x 10(-3) (2.03 x 10(-3), 3.88 x 10(-3)), 3.14 x 10(-2) (1.87 x 10(-2), 4.42 x 10(-2)), 2.27 x 10(-3) (-1.4 x 10(-2),1.81 x 10(-2)), 7.72 x 10(-2) (-0.83 x 10(-2), 0.2374), and -0.2548 (-2.9802, 2.4707), respectively. The activities of CYP1A2 and CYP2C9 were significantly reduced in the present of TMX. CONCLUSION TMX (10 micromol/L) has significant inhibitive effect on the activities of CYP1A2 and CYP2C9, but no significant inhibitive effect on the activities of CYP2C19, CYP2E1 and CYP3A4.
Cytochrome P-450 Enzyme System ; metabolism ; Humans ; Microsomes, Liver ; drug effects ; enzymology ; Xanthones ; pharmacology