The aim of this study was to investigate antimicrobial susceptibilities and macrolide resistance mechanisms of beta-hemolytic viridans group streptococci (VGS) in a tertiary Korean hospital. Minimum inhibitory concentrations (MICs) of seven antimicrobials were determined for 103 beta-hemolytic VGS isolated from various specimens. The macrolide resistance mechanisms of erythromycin-resistant isolates were studied by the double disk test and polymerase chain reaction (PCR). The overall resistance rates of beta-hemolytic VGS were found to be 47.5% to tetracycline, 3.9% to chloramphenicol, 9.7% to erythromycin, and 6.8% to clindamycin, whereas all isolates were susceptible to penicillin G, ceftriaxone, and vancomycin. Among ten erythromycin-resistant isolates, six isolates expressed a constitutive MLSB (cMLSB) phenotype, and each of the two isolates expressed the M phenotype, and the inducible MLSB (iMLSB) phenotype. The resistance rates to erythromycin and clindamycin of beta-hemolytic VGS seemed to be lower than those of non-beta-hemolytic VGS in our hospital, although cMLSB phenotype carrying erm(B) was dominant in beta-hemolytic VGS.
Ceftriaxone/pharmacology ; Chloramphenicol/pharmacology ; Clindamycin/pharmacology ; Cross Infection/*genetics ; *Drug Resistance, Bacterial ; Erythromycin/pharmacology ; Humans ; Immunoenzyme Techniques ; Korea ; Macrolides/*pharmacology ; Penicillin G/pharmacology ; Phenotype ; Polymerase Chain Reaction ; Tetracycline/pharmacology ; Vancomycin/pharmacology ; Viridans Streptococci/*genetics/*metabolism

The aim of this study is to characterize the epidemiological features of typhoid fever, categorized as class 1 notifiable disease in Korea and to analyze the recent change of antimicrobial resistance of Salmonella enterica serotype Typhi isolated nationwide. We retrospectively analyzed the 1,692 culture-proven cases from 1992 to 2000, using the data of the Korean National Institute of Health. The overall incidence of culture-proven typhoid fever was 0.41 per 100,000 population. It occurred all over the country, but the southeastern part of Korean peninsula had the higher incidence rate than other areas. There were several outbreaks suspected, of which two outbreaks were confirmed. The resistance rate against chloramphenicol showed mild increase, but the ampicillin, trimethoprim/sulfamethoxazole, kanamycin, or nalidixic acid resistance remained at the similar levels for the past 9 yr. There were 21 (1.3%) multidrug-resistant (MDR) strains isolated since 1992, and the number of those has increased. Two strains resistant to ciprofloxacin were first identified in Korea.
Ampicillin/pharmacology ; Anti-Bacterial Agents/pharmacology ; Chloramphenicol/pharmacology ; *Drug Resistance, Microbial ; Drug Resistance, Multiple ; Human ; Kanamycin/pharmacology ; Korea ; Nalidixic Acid/pharmacology ; Retrospective Studies ; Salmonella Infections/*epidemiology ; Salmonella enterica/*metabolism ; Seasons ; Serotyping ; Support, Non-U.S. Gov't ; Time Factors ; Trimethoprim/pharmacology

BACKGROUNDIt is still unclear whether viral genetic variability influences response to interferon (IFN)-alpha treatment. Recent reports suggest that IFN-alpha effects may be associated with hepatitis B virus (HBV) post-transcriptional regulation. This study was designed to explore the heterogeneity of HBV post-transcriptional regulatory elements (HPRE) and the relationship between the diversity of HPRE and the response to IFN-alpha treatment.

METHODSThe HPRE sequences from 31 Chinese patients infected with HBV were determined by directly sequencing of polymerase chain reaction (PCR) product, and comparing them to those from Caucasian patients. Subsequently, eukaryotic expression vectors containing HPRE at various points were constructed and transfected into HepG2 cells, which were then exposed to recombinant human cytokines.

RESULTSThe T to C point mutation at nt 1504 and the C to T (G) at nt 1508 in HPRE were found in 21 and 19 patients with chronic hepatitis B, respectively; the C to T point mutation at nt 1509 was found in 17 patients. These point mutations did not exist in the HPRE of the Caucasian patients. The activity of the CAT gene obviously increased in the case of T to C point mutation at nt 1504, but did not change in the case of the C to T (G) mutations at nt 1508 and 1509. The activity of the CAT gene at these point mutations of HPRE could be inhibited by IFN-alpha/gamma and tumor necrosis factor (TNF)-alpha except for the point mutations at nt 1508 of HPRE which may escape the suppression role of IFN-alpha on HPRE.

CONCLUSIONSThere are point mutations between the HPRE of Chinese and Caucasian HBV patients, which might be correlated with response to IFN-alpha. The variation of HPRE might affect the function of HPRE and influence the regulative function of IFN-alpha other than that of IFN-gamma or TNF-alpha on HPRE.

Chloramphenicol O-Acetyltransferase ; metabolism ; Genes, Regulator ; Hepatitis B virus ; drug effects ; genetics ; Hepatitis B, Chronic ; drug therapy ; virology ; Humans ; Interferon-alpha ; pharmacology ; Interferon-gamma ; pharmacology ; Plasmids ; Point Mutation ; Tumor Necrosis Factor-alpha ; pharmacology

The aim is to evaluate the effect of ciprofloxacin and chloramphenicol on anti-BSA antibody production triggered by bovine albumin encapsulated in non-ionic surfactant vesicle, niosomes. Reverse phase evaporation method was adopted to entrap the antigen in colloidal carrier composed of Span 80 and Span 85 followed by simultaneous characterization for particle size, entrapment efficiency and in vitro release. The protein content was determined by Bradford method using UV Visible Spectrophotometer at 595 nm. Humoral immune response was measured in terms of systemic IgG antibody titre by ELISA method. Experimental data indicated that 7 : 3 molar ratio of Span 80 and cholesterol based niosomal formulation possessed maximum (39.8 +/- 2.9)% of soluble protein. Ciprofloxacin markedly (P < 0.05) decreased the antibody titre. In contrast, chloramphenicol did not reduce the antibody titre significantly in comparison to control group (P > 0.05). It is necessary to explore the effect of a vaccine antigen when a candidate is medicated with a therapeutic agent, which might help in programming a new drug management and vaccination programme.
Animals ; Antibody Formation ; drug effects ; Chloramphenicol ; administration & dosage ; pharmacology ; Ciprofloxacin ; administration & dosage ; pharmacology ; Drug Carriers ; Hexoses ; Immunoglobulin G ; blood ; Liposomes ; Male ; Particle Size ; Rats ; Rats, Wistar ; Serum Albumin, Bovine

BACKGROUNDCholera toxin B subunit (CTB) was shown to be a potent adjuvant for protein immunogen, especially when inoculated through mucosal route. We aimed to optimize the expression approach for CTB and thereafter to determine the adjuvant effect on DNA vaccine.

METHODSWild type CTB coding gene was amplified and cloned into prokaryotic expression vector pET-30a, and the recombinant CTB was expressed in the presence of different concentration of chloramphenicol and isopropyl β-D-thiogalactoside. Purified recombinant CTB was mixed with HIV-1 AE2f tat-rev-integrase-vif-nef fusion gene DNA vaccine and female BALB/c mice were vaccinated with a DNA priming-recombinant vaccinia vectored vaccine boosting regimen through intramuscular injection. Interferon γ (IFN-γ) enzyme-linked immunospot (Elispot) assay was used to read out the specific T-cell immunity.

RESULTSChloramphenicol was essential for the efficient expression of recombinant CTB (rCTB) in pET-30a/BL21 (DE3) system and could be optimized at the concentration of 0.625 µg/ml in the presence of chloramphenicol. The purified rCTB could bind with GM1 efficiently. INF-γ Elispot data showed the T-cell response induced in CTB adjuvanted group ((734 ± 240) spot forming cells/10(6) splenocytes) was higher than that induced by non-adjuvanted ((520 ± 150) spot forming cells/10(6) splenocytes), all responses against different antigens were enhanced in parallel.

CONCLUSIONCTB could be efficiently expressed in the presence of chloramphenicol and purified CTB is functional and capable of enhancing the specific T cell responses elicited by DNA vaccine, the mechanism needs to be explored in the future.

Adjuvants, Immunologic ; pharmacology ; Animals ; Blotting, Western ; Chloramphenicol ; pharmacology ; Cholera Toxin ; metabolism ; Electrophoresis, Polyacrylamide Gel ; Escherichia coli ; drug effects ; metabolism ; Female ; Mice ; Mice, Inbred BALB C ; Recombinant Fusion Proteins ; genetics ; immunology ; metabolism ; Vaccines, DNA ; genetics ; immunology ; metabolism

BACKGROUND: Bacteroides fragilis group organisms are the most frequently isolated anaerobes in human infections. Increasing resistance to various antimicrobial agents is a significant problem in choosing appropriate antimicrobial agents to treat anaerobic infections. Periodic monitoring of the regional resistance trends of B. fragilis group isolates is needed. METHODS: A total of 466 nonduplicate clinical isolates of B. fragilis group organisms (276 B. fragilis, 106 Bacteroides thetaiotaomicron, and 84 other B. fragilis group organisms) were collected during the 8-yr period from 1997 to 2004 in a Korean university hospital. Minimum inhibitory concentrations to various antimicrobial agents were determined by the CLSI agar dilution method. RESULTS: Eight isolates were resistant to imipenem. Additionally, the resistance rates to cefotetan were decreased in B. thetaiotaomicron, while those for clindamycin were significantly increased compared to the rates found in previous studies. Depending on species, resistance rates were 1-4% for imipenem, 1-6% for piperacillin-tazobactam, 4-11% for cefoxitin, 33-49% for piperacillin, 14-60% for cefotetan, and 51-76% for clindamycin. No isolates were resistant to chloramphenicol or metronidazole. CONCLUSIONS: Piperacillin-tazobactam, cefoxitin, imipenem, chloramphenicol, and metronidazole are still active against B. fragilis group isolates, while clindamycin no longer has a value as an empirical therapeutic agent in Korea. Furthermore, this study identified the first imipenem-resistant B. fragilis group isolates in Korea.
Anti-Bacterial Agents/pharmacology ; Bacteroides/classification/*drug effects/isolation & purification ; Bacteroides fragilis/drug effects/isolation & purification ; Cefoxitin/pharmacology ; Chloramphenicol/pharmacology ; *Drug Resistance, Multiple, Bacterial ; Humans ; Imipenem/pharmacology ; Metronidazole/pharmacology ; Microbial Sensitivity Tests ; Penicillanic Acid/analogs & derivatives/pharmacology ; Piperacillin/pharmacology ; Republic of Korea

We made fusion protein of fastatin and FIII 9-10, termed tetra-cell adhesion molecule (T-CAM) that can interact simultaneously with alphavbeta3 and alpha5beta1 integrins, both playing important roles in tumor angiogenesis. T-CAM can serve as a cell adhesion substrate mediating adhesion and migration of endothelial cells in alphavbeta3 and alpha5beta1 integrin-dependent manner. T-CAM showed pronounced anti-angiogenic activities such as inhibition of endothelial cell tube formation, endothelial cell proliferation, and induction of endothelial cell apoptosis. T-CAM also inhibited angiogenesis and tumor growth in mouse xenograft model. The anti-angiogenic and anti-tumoral activity of molecule like fastatin could be improved by fusing it with integrin-recognizing cell adhesion domain from other distinct proteins. The strategy of combining two distinct anti-angiogenic molecules or cell adhesion domains could facilitate designing improved anticancer agent of therapeutic value.
Angiogenesis Inhibitors/chemistry/*pharmacology ; Animals ; Antineoplastic Agents/chemistry/*pharmacology ; Base Sequence ; Benzocaine/chemistry/*pharmacology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Chloramphenicol/chemistry/*pharmacology ; DNA Primers ; Drug Combinations ; Factor VIII/chemistry/*pharmacology ; Humans ; Integrin alpha5beta1/*physiology ; Integrin alphaVbeta3/*physiology ; Male ; Mice ; Mice, Inbred BALB C ; Nitrofurazone/chemistry/*pharmacology ; Recombinant Fusion Proteins/chemistry/*pharmacology

A series of new coumarin-based benzotriazole derivatives were successfully synthesized via a multi-step sequence of cyclization, etherification and N-alkylation, and were confirmed by 1H NMR, IR, MS spectra as well as elemental analyses. All these synthesized coumarin compounds were evaluated for in vitro antimicrobial activities against four Gram-positive bacteria, four Gram-negative bacteria and three fungi by two fold serial dilution technique. The bioactive assay showed that all these prepared coumarin benzotriazoles could inhibit the growth of the tested bacterial and fungal strains. Title compounds 11a-11e and 13a-13c were more active than chloromycin on Proteus vulgaris ATCC 6896. Coumarin benzotriazoles 11a and 11b displayed comparable antibacterial efficacy against Staphylococcus aureus ATCC 25923 and Micrococcus luteus ATCC 4698 in comparison with reference drug chloromycin. Compared to fluconazole, compounds 11a-11d displayed stronger inhibition on Aspergillus fumigatus ATCC 96918. Moreover, coumarin-based benzotriazoles in combination with antibacterial chloromycin or antifungal fluconazole, showed notable antimicrobial efficacy with less dosage and broader antimicrobial spectrum. More importantly, fluconazole-insensitive A. fumigatus and methicillin-resistant Staphylococcus aureus N 315 (MRSA) were sensitive to these combined drugs.
Anti-Bacterial Agents ; chemical synthesis ; chemistry ; pharmacology ; Antifungal Agents ; chemical synthesis ; chemistry ; pharmacology ; Aspergillus fumigatus ; drug effects ; Chloramphenicol ; pharmacology ; Coumarins ; chemical synthesis ; chemistry ; pharmacology ; Drug Synergism ; Fluconazole ; pharmacology ; Fungi ; drug effects ; Gram-Negative Bacteria ; drug effects ; Gram-Positive Bacteria ; drug effects ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; Staphylococcus aureus ; drug effects ; Triazoles ; chemical synthesis ; chemistry ; pharmacology

American ginseng (AG) has been demonstrated to inhibit breast cancer cell growth in vitro. p21 protein, a universal cell cycle inhibitor, binds cyclin-CDK complexes, an important mechanism in cell cycle regulation. The purpose of this investigation was to determine if AG induces p21 gene expression in hormone sensitive (MCF-7) and insensitive (MDA-MB-231) breast cancer cell lines. Cells grown in steroid stripped medium (SSM) were treated with AG, 17-beta-estradiol (E2), genistein or cycloheximide (CHX). Northern blot analyses were performed using human p21Cip1 and 36B4 cDNA probes. Cell lines were transiently transfected with select mouse p21 CAT reporter constructs, including those lacking a p53 binding site. Cell cycle analyses was performed by FACScan. The results revealed that AG induced p21 mRNA expression in MCF-7 and MDA-MB-231 cells (p=0.0004; p< or =0.0001, respectively). Neither E2 nor genistein alter p21 mRNA expression. CHX, a protein synthesis inhibitor, did not block p21 mRNA expression induced by AG, indicating that p21 is induced as an immediate early gene. AG activated p21 reporter constructs in transfected cells, independent of p53 binding sites. The cell cycle proliferative phase was significantly decreased by AG and increased by E2 (p< or =0.0001). AG may inhibit breast cancer cell growth by transcriptional activation of the p21 gene, independent of p53.
Animal ; Binding Sites ; Breast Neoplasms ; Cell Division/drug effects ; Chloramphenicol O-Acetyltransferase/genetics ; Cyclins/*genetics ; Female ; Genes, Reporter ; HT29 Cells ; Human ; Mice ; *Panax ; Plant Extracts/pharmacology ; Protein p53/metabolism ; *RNA, Messenger ; *Trans-Activation (Genetics) ; Tumor Cells, Cultured

OBJECTIVETo investigate the antibiotics-resistance type and molecular epidemiology of Streptococcus pneumoniae isolated from children in Hangzhou.

METHODSThe sensitivities of 323 strains of Streptococcus pneumoniae to 9 antibiotics were determined in vitro by Kirby-Bauer diffuse methods, and MICs of penicillin and cefotaxime were determined by E-test methods.

RESULTSAmong all 323 strains isolated from children during the period from August 2001 to July 2002, 136 strains (42.1%) were sensitive to penicillin, while 57 strains (17.7%) were penicillin-resistant. Penicillin MICs ranged from 0.012 microg/ml to 4.0 microg/ml. All the strains were sensitive to cefotaxime and its MICs ranged from 0.012 microg/ml to 4.0 microg/ml. The most resistant antibiotic was erythromycin and it's resistant-rate was as high as 90.7%, followed by tetracycline (87.6%), trimethoprim-sulfamethoxazole (48.6%) and chloromycetin (14.9%). Totally 197 strains (61.0%) were multi-drug-resistant pneumococci and most of them were resistant to trimethoprim-sulfamethoxazole, erythromycin and tetracycline at the same time. Two strains (0.6%) were resistant to rifampin and none was resistant to vancomycin and ofloxacin. BOX PCR typing was carried out and no overwhelming fingerprinting pattern was found among penicillin resistant Streptococcus pneumoniae strains which were isolated from patients, while the banding patterns were always similar or identical among the strains isolated from the same specimen or from the same patient at different time, respectively.

CONCLUSIONThe antibiotics-resistant rate of pneumococci was high in Hangzhou, but the third-generation cephalosporins were still the best antibiotics against Streptococcus pneumoniae. One child could be infected or colonized by more than one pneumococci clone at the same or different time.

Anti-Bacterial Agents ; pharmacology ; therapeutic use ; Cefotaxime ; pharmacology ; therapeutic use ; Child, Preschool ; China ; Chloramphenicol ; pharmacology ; therapeutic use ; Drug Resistance, Bacterial ; drug effects ; Erythromycin ; pharmacology ; therapeutic use ; Female ; Humans ; Infant ; Male ; Microbial Sensitivity Tests ; Ofloxacin ; pharmacology ; therapeutic use ; Penicillins ; pharmacology ; therapeutic use ; Pneumococcal Infections ; drug therapy ; microbiology ; Respiratory Tract Infections ; drug therapy ; microbiology ; Rifampin ; pharmacology ; therapeutic use ; Streptococcus pneumoniae ; classification ; drug effects ; isolation & purification ; Tetracycline ; pharmacology ; therapeutic use ; Trimethoprim ; pharmacology ; therapeutic use