Antibiotics, Antineoplastic ; pharmacology ; Apoptosis ; Cell Line, Tumor ; Doxorubicin ; pharmacology ; Gangliosides ; Humans ; NF-kappa B ; metabolism

Aeromonas hydrophila infection has been increasingly found, in particular among patients with various underlying diseases. Many characteristics of this organism are quite similar to those of Enterobacteriaceae and Vibrio, making an accurate identification difficult. In a period of 2 years, the authors obtained a total of 27 isolates of A. hydrophila from clinical materials, and their cultural and biochemical characteristics are herewith reported. Some of the most important clues to suspect this organism were a wide zone of complete hemolysis on blood agar, partially alkaline slant, acid butt, and small amount of gas in trip1e sugar iron agar (TSI), weak indole reaction, and negative ornithine decarboxylase in motility indole ornithine medium (MIO), and usually positive citrate utilization. It is concluded that the identification of this organism should be possible on the basis of deoxyribonuclease (DNase), oxidase, and a few other tests. Our isolates showed a similar antibiotic susceptibility to those reported in other countries; i.e., a11 were resistant to ampicillin and most were susceptible to other antibiotics, excluding cephalothin.
Aeromonas/drug effects ; Aeromonas/isolation & purification* ; Aeromonas/physiology ; Antibiotics/pharmacology ; Culture Media ; Human ; Microbial Sensitivity Tests

BACKGROUNDBleomycin-induced fibrosis is extensively used to model aspects of the pathogenesis of interstitial pulmonary fibrosis. This study aimed to determine the benefic effects and mechanisms of simvastatin on bleomycin-induced pulmonary fibrosis in mice.

METHODSBleomycin-induced pulmonary fibrosis mice were administered with simvastatin in different doses for 28 days. We measured inflammatory response, fibrogenic cytokines and profibrogenic markers in both bleomycin-stimulated and control lungs, and correlated these parameters with pulmonary fibrosis.

RESULTSSimvastatin attenuated the histopathological change of bleomycin-induced pulmonary fibrosis and prevented the increase of lung hydroxyproline content and collagen (I and III) mRNA expression induced by bleomycin. Moreover, simvastatin down-regulated the increased expression of transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor (CTGF) induced by bleomycin at both gene and protein levels. Simultaneously, the accumulation of neutrophils and lymphocytes and the increased production of tumor necrosis factor-alpha (TNF-alpha) in bronchial alveolar lavage fluid were inhibited by simvastatin in early inflammatory phase after bleomycin infusion. The higher dose of simvastatin was associated with a more significant reduction in these inflammatory and fibrotic parameters. Furthermore, the inactivation of p38, RhoA and Smad2/3 signaling pathways was observed during simvastatin administration.

CONCLUSIONSSimvastatin attenuated bleomycin-induced pulmonary fibrosis, as indicated by decreases in Ashcroft score and lung collagen accumulation. The inhibitory effect of simvastatin on the progression of pulmonary fibrosis may be demonstrated by reducing inflammatory response and production of TGF-beta1 and CTGF. These findings indicate that simvastatin may be used in the treatment of pulmonary fibrosis.

Animals ; Antibiotics, Antineoplastic ; Bleomycin ; Mice ; Mice, Inbred C57BL ; Pulmonary Fibrosis ; chemically induced ; metabolism ; pathology ; Simvastatin ; pharmacology

Hyaluronan (HA), a natural glycoaminoglycan featuring an extracellular matrix, has been suggested as an effective biocompatible material. In this study, the effectiveness of HA microparticles as a carrier system for antibiotics was evaluated, and their physicochemical characteristics were determined. Microparticles were fabricated by the gelation of sulfadiazine (SD) loaded HA solution with calcium chloride through either a granulation (GR-microparticles) or encapsulation (EN-microparticles) process, and atelocollagen was incorporated into the microparticles as an additive in order to improve their physical properties. The characteristics of the microparticles were examined by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and swelling test. In vitro release experiments were performed for 7 days and the released amount of SD was determined using high-performance liquid chromatography (HPLC). Microscopic observations revealed that the collagen incorporated HA particles had a more compact surface than the HA particles. DSC analysis determined a loss of SD crystallinity in the particles. Calcium chloride retarded the swelling of particles, whereas the loaded drug contents did not affect this property. Both GR-and EN-microparticles sustained SD release with initial bursting effect. SD release from EN-microparticles was faster than from GR- microparticles. In addition, the release rate was dependent on the SD content in the microparticles. These results suggest that collagen modified HA microparticles have a potential as a release rate controlling material for crystalline drugs such as SD.
Antibiotics/*administration & dosage ; Calcium Chloride/pharmacology ; Collagen/*pharmacology ; *Drug Carriers ; Hyaluronic Acid/*administration & dosage ; Sulfadiazine/administration & dosage

Enterococci have emerged as a major nosocomial pathogen and as an ever-increasing problem in antimicrobial resistance. They are ubiquitous in the intestinal flora of humans and animals and inherently resistant to a wide array of antimicrobial agents, and, more alarmingly, they seem to have a potential facility for acquiring new resistance determinants, including beta-lactamase production, high-level resistance to aminoglycosides, and recently, glycopeptide resistance. Collectively, all of these properties make enterococci one of most difficult nosocomial pathogens to treat and control today. The purpose of this review was to examine the epidemiology, the mechanisms, and laboratory detection of resistance of enterococci to the two major groups of antibiotics: aminoglycosides and glycopeptides.
Aminoglycosides/pharmacology ; Antibiotics, Glycopeptide/pharmacology ; Drug Resistance, Microbial/physiology* ; Enterococcus/physiology* ; Enterococcus/drug effects ; Epidemiologic Methods ; Human

This study was aimed to investigate the molecular mechanism of doxorubicin resistance in multiple myeloma cell line and certify the effect of Notch signal over-expression on drug resistance of myeloma cells. The doxorubicin RPMI 8226 cell line (RPMI8226/DOX) was established by culturing 8226 cells with continuous low concentration and intermittent gradually-increasing-concentration of doxorubicin in vitro, the mRNA expression of Notch2,Jagged1, Jagged2, HES1 were measured by RT-PCR and the P-170 protein expression was detected by Western blot in RPMI 8226 cell line; the changes of IL-6 and VEGF were tested by ELISA. The results showed that the Notch mRNA expression (Notch2, Jagged1, Jagged2 increased gradually along with the increase of chemotherapeutic drug resistance, but the expression of HESI mRNA gradually decreased along with the increase of drug resistance. The expression level of P-170 protein was upregulated gradually along with the increase of drug resistance. The level of VEGF and IL-6 in culture supernatants of RPMI8226/DOX was higher than that in RPMI 8226. It is concluded that the establishment of RPMI 8226/DOX cell line is a useful model to analyze the mechanism of chemotherapeutic drug resistance in multiple myeloma, Notch activation is closely correlated with the drug resistance of multiple myeloma and Notch signaling may to be used as a new target for multiple myeloma treatment.
Antibiotics, Antineoplastic ; pharmacology ; Cell Line, Tumor ; Doxorubicin ; pharmacology ; Drug Resistance, Neoplasm ; Humans ; Interleukin-6 ; Multiple Myeloma ; metabolism ; pathology ; Signal Transduction

The emergence of multi-drug resistant gram-positive cocci such as methicillin-resistant (MR) staphylococci, vancomycin-resistant (VR) enterococci, and vancomycin-intermediate resistant S. aureus (VISA) has given new urgency to the development of new antimicrobial agents. One of these is quinupristin/dalfopristin (Q/D). We decided to determine the susceptibility of gram-positive cocci isolated at two university hospitals in Seoul to Q/D and compare the results with eight other antimicrobial agents. We investigated 120 isolates of S. aureus including 49 MRSAs and one VISA, 120 isolates of coagulase negative staphylococci (CNS), 64 E. faecalis and 56 E. faecium, including seven strains of VR E. faecium. Minimum inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) for several antimicrobials, including vancomycin and Q/D, were determined by broth microdilution. All S. aureus including VISA were susceptible to Q/D. Q/D MIC90 for both methicillin-susceptible S. aureus (MSSA) and MRSA was 0.25 g/mL. 49 (87.5%) of 56 E. faecium including six of seven VR E. faecium were susceptible to Q/D. E. faecalis were not susceptible to Q/D (only 1.5% susceptible), but were inhibited by ampicillin (94% susceptible) or vancomycin (95%). CNS was susceptible to Q/D (96% susceptible) and vancomycin (100% susceptible). One of 38 staphylococci and two of 17 E. faecium were tolerant to Q/D. In conclusion, Q/D showed excellent activity against all species of gram-positive cocci including MRSA, VISA, and VR E. faecium except E. faecalis, and may provide a valuable option for the treatment of infections caused by these emerging nosocomial pathogens of gram-positive cocci.
Antibiotics/pharmacology* ; Antibiotics, Peptide/pharmacology* ; Coagulase/analysis ; Enterococcus faecalis/drug effects ; Enterococcus faecium/drug effects ; Human ; Korea ; Microbial Sensitivity Tests* ; Staphylococcus/enzymology ; Staphylococcus/drug effects ; Staphylococcus aureus/drug effects ; Support, Non-U.S. Gov'tn ; Virginiamycin/pharmacology* ; Virginiamycin/analogs & derivatives*

Campylobacter fetus subsp. fetus is a rare human pathogen, but can cause serious extraintestinal infections. Effective antimicrobial agent is required for the therapy, but we have very limited knowledge on the susceptibility of the organism. In this study, the susceptibility of 25 isolates of the organism to 14 antimicrobial agents was tested by an agar dilution method. Antimicrobial agents with low MIC ranges, in micrograms/ml, were: meropenem Y or = 0.25, dirithromycin < or = 0.5, gentamicin > or = 1, amikacin, ofloxacin, tetracycline and erythromycin < or = 2. The MIC range of cefepime was 0.5-8 micrograms/ml, but those of other beta-lactams were relatively high. All of the isolates were interpreted to be susceptible to cefepime, meropenem, amikacin, gentamicin, ofloxacin, tetracycline and dirithromycin. A significant proportion of the isolates were either intermediate or resistant to ampicillin, cephalothin, cefotaxime, aztreonam, loracarbef and erythromycin. In conclusion, the organism remains susceptible to aminoglycosides and tetracycline. Greater in vitro activity of meropenem, ofloxacin and dirithromycin require clinical evaluation.
Antibiotics/*pharmacology ; Blood/*microbiology ; Campylobacter fetus/*drug effects/isolation & purification ; Human ; Microbial Sensitivity Tests ; Synovial Fluid/*microbiology

OBJECTIVETo evaluate the effect of combination of glutamine (GLN) and mitomycin C (MMC) on the human gastric carcinoma cell line MGC-803 in vitro.

METHODSThe effects of GLN and MMC were measured by MTT assay, and the interaction between the two agents was evaluated by the median-effect principle. Flow cytometry was used for cell cycle analysis.

RESULTSGLN did not significantly stimulate the cell growth in vitro. High-concentration of GLN could inhibit the cell growth. MMC could effectively inhibit the cell growth in a time-dependent manner. The interaction of these two agents showed a weak antagonistic activity (1 < CI < 1.2703). MMC induced remarkable S-phase arrest. Low-dose GLN has limited effect on the S-phase arrest of MMC, while high-dose GLN significantly attenuated the S-phase arrest and lowered the proliferation index of MGC-803 cell.

CONCLUSIONSCombination of GLN and MMC has a a weak and dose-dependent antagonistic activity in the treatment of gastric carcinoma cell line MGC-803. The combination of high-dose MMC and low-dose GLN may achieve better efficacy.

Adenocarcinoma ; pathology ; Antibiotics, Antineoplastic ; pharmacology ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Drug Synergism ; Glutamine ; pharmacology ; Humans ; Mitomycin ; pharmacology ; Stomach Neoplasms ; pathology

With the emergence of drug resistant tuberculosis, it is very urgent to find novel anti-tuberculosis drugs, especially novel anti-drug-resistant tuberculosis drugs. Because of the slow growth and the need to work in a biosafty environment of Mycobacterium tuberculosis, the development of evaluation of drug effect is severely impeded. In order to solve these issues, non-pathogenic fast-growing Mycobacterium smegmatis is introduced as test organism. The inhA is one of a target of isoniazid (INH) overexpression or mutation of this gene in Mycobacterium tuberculosis conferring resistant to INH. A recombinant plasmid bearing inhA was constructed and electroporated into Mycobacterium smegmatis, using shuttle expression vector pMV261. Transformants were induced to express a protein of inhA, identified by SDS-PAGE. Results show that Mycobacterium smegmatis containing inhA plasmids exhibited 100-fold or greater increased resistance to INH, but it conferred no increased resistance to others first-line anti-tuberculosis drugs. Resazurin microtiter assay plate testing of Mycobacterium smegmatis susceptibility to drugs is a rapid, simple, and inexpensive method and could decrease color background of drugs by detecting fluorescence. It will be benefit for high-throughout screening of drugs of anti-isoniazid-resistant Mycobacteria.
Anti-Bacterial Agents ; pharmacology ; Antibiotics, Antitubercular ; pharmacology ; Antitubercular Agents ; pharmacology ; Bacterial Proteins ; genetics ; metabolism ; Drug Resistance, Bacterial ; Electroporation ; Ethambutol ; pharmacology ; Isoniazid ; pharmacology ; Microbial Sensitivity Tests ; Mycobacterium smegmatis ; drug effects ; genetics ; metabolism ; Oxidoreductases ; genetics ; metabolism ; Plasmids ; Rifampin ; pharmacology ; Streptomycin ; pharmacology