Although the decreased susceptibility of gonococci to penicillin and tetracycline is a worldwide problem in the treatment of gonorrhea, the gonococci in the West Pacific region are particulary notorious in their resistance. Using a plate dilution method, susceptibility of the gonococci isolated at this institution during 1970 to 1975 was tested to penicillin and tetracycline, which are the most widely used antibiotics for the treatment of gonorrhea. The data of this susceptibility, together with that of the strains isolated during 1966 to 1969 from prostitutes, were analyzed and herewith reported. The range of minimum inhibitory concentration (MIC) of penicillin was 0.01 to 2.0U/ml. Among the 191strains, 87.9% required MIC of 1.0U/ml and over, and 29.3% required 1.0U/ ml and over. The range of MIC of tetracycline was from 0.125 to over 2 microgram/ml. Among the 120 strains, 60% required MIC of 1 microgram/ml and over. This in vitro evidence indicates wide prevalence of less susceptible strains which are difficult to cure with conventional doses of penicillin or with tetracycline. Comparison of the degree and the frequency of less susceptible strains by the year of isolation showed some variation, which may however have been induced by the difference of sources, rather than by the difference of time of isolation.
Neisseria gonorrhoeae/drug effects* ; Penicillins/pharmacology* ; Tetracyclines/pharmacology*

We adopted firstly the dextran-coated charcoal(DCC) and SP methods to detect estrogen receptor (ER) expression of bone tissue in ovariectomized(OVX) rats. The results demonstrate that in OVX rats, XW630 can significantly promote ER expression in bone tissue and increase the ER content. XW630 is superior to estrone in effectiveness. The results also reveal that the ER expression in OVX rat bone tissue decreases with the lapse of time, indicating that the expression of ER depends on the existence of estrogen.
Animals ; Bone and Bones ; metabolism ; Estrogens, Conjugated (USP) ; pharmacology ; Female ; Ovariectomy ; Piperazines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Estrogen ; biosynthesis ; Tetracycline ; pharmacology ; Tetracyclines

AIMTo study the effect of XW630 on expression of pro-oncogene c-myc in the long bones of fetal mice in vitro for postulating the mechanism by which XW630 exerts its effect on bone.

METHODSThe fetuses of pregnant mice were removed on day 16 of gestation, the long bones of the forelimbs of female fetal mice were freed of muscle and soft tissue and cultured in a specific device for 48 h in BGJb medium treated with 1 x 10(-7), 1 x 10(-8) and 1 x 10(-9) mol.L-1 XW630 in the final medium. After cultured for 48 h, the long bones were harvested and immunohistochemical analysis was performed for determination of c-Myc protein expression in epiphyseal plates. The areas of positive cells in the resting zone, proliferative zone and hypertrophic zone in epiphyseal plate were determined under image analytic system.

RESULTSWhen the concentration of XW630 in the medium was 1 x 10(-9) mol.L-1, the area of c-Myc positive cells increased in the proliferative zone compared with 1 x 10(-9) mol.L-1 in the estrone group, significant increase was also observed in the resting zone compared with the control group. When the concentration of XW630 in medium was 1 x 10(-8) or 1 x 10(-7) mol.L-1, stronger expression than that in the control group and the estrone group at the same concentration was observed in each of the three zones.

CONCLUSIONThe estrogenic effect of XW630 on bone was stronger than that of estrone. XW630 may promote proliferation and differentiation of chondroncytes by promoting c-Myc protein expression in chondroncytes. Thus, endochondral bone formation was enhanced.

Animals ; Chondrocytes ; metabolism ; Culture Techniques ; Estrone ; pharmacology ; Female ; Fetus ; Mice ; Piperazines ; pharmacology ; Pregnancy ; Proto-Oncogene Proteins c-myc ; metabolism ; Tetracyclines ; pharmacology ; Ulna ; drug effects ; metabolism ; Up-Regulation ; drug effects

This study was performed to investigate the mechanism of an anti-osteoporosis new drug XW630 for promoting the osteogenic action. Osteoblast clone was cultivated from SD adult rat calvaria in vitro, the estrogen receptor messenger RNA(ERmRNA) expression in the osteoblasts of rats was detected directly with high-sensitive RT-PCR firstly. The results indicated that XW630 can significantly promote ERmRNA expression in osteoblasts in the time-dependent manner. Being superior to other two kinds of estrogen in the same concentration (10(-6) mol/L), XW630 probably plays an important role in the bone pathogenesis by means of ER gene regulatory functions.
Animals ; Cells, Cultured ; Female ; Gene Expression ; Osteoblasts ; drug effects ; metabolism ; Piperazines ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Estrogen ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tetracycline ; pharmacology ; Tetracyclines

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

PURPOSE: The detection of high-level tetracycline-resistant strains of Neisseria gonorrhoeae (TRNG) can make important epidemiological contributions that are relevant to controlling infections from this pathogen. In this study, we aimed to determine the incidence of TRNG isolates over time and also to investigate the characteristics and genetic epidemiology of these TRNG isolates in Korea. MATERIALS AND METHODS: The antimicrobial susceptibilities of 601 isolates of N. gonorrhoeae from 2004 to 2011 were tested by standard Clinical and Laboratory Standards Institute methods. To determine the molecular epidemiological relatedness, N. gonorrhoeae multi-antigen sequence typing was performed. RESULTS: The incidence of TRNG increased from 2% in 2004 to 21% in 2011. The minimum inhibitory concentration distributions of ceftriaxone and susceptibility of ciprofloxacin in TRNG were different from non-TRNG and varied according to the year of isolation. Most of the TRNG isolates collected from 2004 to 2007 exhibited genetic relatedness, with sequence type (ST) 1798 being the most common. From 2008 to 2011, the STs of the isolates became more variable and introduction of genetically unrelated TRNG were noted. CONCLUSION: The increased incidence of TRNG strains until 2007 appears to be due, at least in part, to clonal spread. However, we propose that the emergence of various STs since 2008 could be associated with foreign import.
Anti-Bacterial Agents/*pharmacology ; Ceftriaxone/pharmacology ; Ciprofloxacin/pharmacology ; DNA, Bacterial/analysis ; Drug Resistance, Multiple, Bacterial/*genetics ; Gonorrhea/drug therapy/epidemiology/microbiology ; Humans ; Incidence ; Microbial Sensitivity Tests ; Molecular Epidemiology ; Neisseria gonorrhoeae/*drug effects/*genetics/isolation & purification ; Republic of Korea/epidemiology ; Sequence Analysis, DNA ; Tetracycline/pharmacology ; Tetracyclines/*pharmacology