The nonsteroidal anti-inflammatory drugs have been shown to support cytoprotection of cells by shifting cells toward a quiescent state (G(0)/G(1)). Extracellular signal-regulated kinase (ERK) is required for cells to pass from G(1) phase into S phase, and macrolide antibiotics can inhibit ERK1/2 phosphorylation. However, previous reports suggest that macrolide antibiotics do not affect cell growth in bronchial epithelial cells. Therefore, we studied normal human bronchial epithelial (NHBE) cells to determine whether clarithromycin (CAM) suppresses ERK, delays bronchial epithelial cells from progressing to S phase, and delays cell growth. Exposure to CAM at 10 microg/ml daily over 4 days irreversibly decreased the cell proliferation with and without growth supplements (P < 0.0001). CAM also inhibited ERK1/2 phosphorylation over the first 90 min of exposure (P < 0.05 for 30 min, P < 0.0001 for 60 min, and P < 0.01 for 90 min) and decreased the ratio of phosphorylated ERK1/2 (pERK1/2) to total ERK1/2 (tERK1/2) (P < 0.0001). Incubation with CAM for 48 h increased the proportion of cells in G(1) phase (means +/- standard deviations) from 63.5% +/- 0.9% to 79.1% +/- 1.4% (P < 0.0001), decreased that in S phase from 19.8% +/- 1.2% to 10.0% +/- 2.1% (P < 0.01), and decreased that in G(2)/M phase from 16.7% +/- 0.4% to 11.0% +/- 0.8% (P < 0.001). In contrast, the ratio of pMEK1/2 to tMEK1/2 was not altered after exposure to CAM. These results suggest that macrolide antibiotics can delay the progression of NHBE cells from G(1) phase to S phase and can slow cell growth, probably through the suppression of ERK1/2.
Although no regimen can eradicate in 100% of patients, factors that may affect the eradication rates have been poorly studied.
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On the whole rates of H. pylori antibiotic resistance were 47.22% (30.5%-75.02%) for metronidazole, 19.74% (5.46%-30.8%) for clarithromycin, 18.94% (14.19%-25.28%) for levofloxacin, and 14.67% (2%-40.87%) for amoxicillin, 11.70% (0%-50%) for tetracycline, 11.5% (0%-23%) for furazolidon and 6.75% (1%-12.45%) for rifabutin. The frequency of tetracycline, metronidazole and amoxicillin resistance was higher in Africa, while clarithromycin and levofloxacin resistance was higher in North America and Asian, respectively.
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This study was conducted to evaluate the activity of levofloxacin in comparison with a range of antibacterial agents against recent isolates obtained consecutively from patients with community-acquired pneumonia (CAP) or acute exacerbation of chronic bronchitis (AECB) during the period 1995 to 1996. Susceptibility testing was carried out by either microdilution or the Etest, and interpreted according to NCCLS breakpoints. The activity of levofloxacin was compared with that of amoxycillin, amoxycillin-clavulanate, cefuroxime, cefixime, erythromycin, roxithromycin, clarithromycin, azithromycin, ofloxacin and ciprofloxacin. Clinically significant numbers of bacteria were recovered from 31 CAP and 94 AECB specimens. The predominant bacterial species in the CAP specimens were Streptococcus pneumoniae (21 isolates) and Haemophilus influenzae (four isolates). The AECB isolates mainly consisted of S. pneumoniae (38%), Moraxella catarrhalis (26%), H. influenzae (19%) and Pseudomonas aeruginosa (10%). The overall percentage susceptible of the isolates for each antibiotic was: amoxycillin, 64%; amoxycillin-clavulanate, 89%; cefuroxime, 87%; cefixime, 78%; erythromycin, 85%; roxithromycin, 87%; clarithromycin, 87%; azithromycin, 85%; ofloxacin, 95%; ciprofloxacin, 95%; and levofloxacin, 97%. The activities of levofloxacin and the other agents were also compared against 40 S. pneumoniae isolates, of which 20 were penicillin-non-susceptible, recovered from CAP and AECB specimens during the period 1994 to 1996. These strains were all susceptible to levofloxacin, but only 50% were susceptible to ciprofloxacin and 80% to ofloxacin. Twenty M. catarrhalis, 20 H. influenzae and 20 methicillin-susceptible S. aureus isolates were also all susceptible to levofloxacin. Furthermore, 20 community-acquired P. aeruginosa isolates showed similar percentage susceptible rates to levofloxacin and ciprofloxacin. These in-vitro results suggest that levofloxacin may be useful in the treatment of community-acquired lower respiratory tract infections.
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Prolonged administration of two antibiotics (of which one must be clarithromycin) in addition to surgery was well-tolerated and could be useful in patients with NTMB neck lymphadenitis.
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Biological treatments, chemoimmunotherapy, and radiotherapy are associated with excellent disease control in both gastric and extragastric mucosa-associated lymphoid tissue (MALT) lymphomas. Systemic treatment approaches with both oral and i.v. agents are being increasingly studied, not only for patients with disseminated MALT lymphoma, but also for those with localized disease. To date, however, recommendations for the use of available systemic modalities have not been clearly defined.
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The estimated probability of being ulcer-free at 6 months was 0.56 (95% CI 0.47-0.65) on eradication treatment and 0.53 (0.44-0.62) on on control treatment (p=0.80). Time to treatment failure did not differ between groups for ulcers or dyspepsia alone, per-protocol analysis, or final H. pylori status. 66% (58-74) of the eradication group compared with 14% (8-20) of the control group had a final negative H. pylori result (p<0.001). Fewer baseline gastric ulcers healed among eradication-treatment patients than among controls (72 vs 100% at 8 weeks, p=0.006).
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The aim of this study was to develop an efficient method of preparing less irritant clarithromycin-loaded liposomes (CLA-Lip) for injection with a high drug loading and to evaluate their physicochemical characteristics before and after lyophilization. CLA-Lip were prepared using the film-dispersion method with sodium cholesterol sulfate (SCS) and n-hexyl acid as the regulators and then lyophilized. The liposomes were characterized in terms of their size, size distribution, zeta potential, morphology, in vitro release, haemolysis, and lyophilization and irritation testing was carried out. The TEM images revealed that the structure of the CLA-Lip were multilamellar and of a regular size of around 100 nm. In addition, the lyophilized CLA-Lip were characterized by DSC and Infrared spectroscopy to confirm the structure. H-bonding and salt-forming reactions were used to ensure that clarithromycin (CLA) was stably encapsulated in the liposomes. This method provided a 30-fold increase in the concentration of clarithromycin relative to that in aqueous solution. Sucrose was found to be the best protective agent and was added in an amount of 12.5% (w/v). According to the mouse scratch test and the rat paw lick test, the pain of CLA-Lip was significantly reduce by approximately 80% compared with the solution of clarithromycin phosphate. In addition, rabbit ear vein experiments produced similar results. These findings suggested that CLA-Lip was a stable delivery system with less irritation, which should be extremely suitable for clinical application.
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Antimicrobial resistance is one of the main obstacles for an effective eradication of H. pylori infection.