The impact of two different pharmaceutical preparations on the pharmacokinetics of roxithromycin was investigated in healthy human volunteers.
Compared with normal control, TGF-β1 secretion was significantly increased in asthmatic ASMCs; meanwhile, TGF-β1 promoted ASMCs proliferation (P < 0.05). However, ASMCs proliferation was remarkably inhibited by RXM, β-CD, PD98059 and wortmannin (P < 0.05). Moreover, the expressions of p-ERK1/2 and p-AKT were increased and peaked at 20 min after TGF-β1 stimulation, and then suppressed by RXM. Further, caveolin-1 level was down-regulated by TGF-β1 and up-regulated by inhibitors and RXM.
Roxithromycin (RXM) is a new macrolide antibiotics, with anti-allergic properties, the mechanisms of which action has not been well understood. The effect of RXM-treatment on the induction of interleukin 2 (IL-2) responsiveness by Dermatophagoides farinase (Df)-stimulated lymphocytes was studied in patients with bronchial asthma. RXM alone has almost no effect on lymphocyte activation. Patient's lymphocytes treated with 10 to 400 micrograms/ml doses of RXMs failed to generate Df-induced IL-2 responsiveness in a dose-dependent manner. The target cells for suppressive effect of RXM were antigen-presenting cells such as macrophages and dendritic cells rather than responder T cells. PPD-induced IL-2 responsiveness was also suppressed by the treatment, but the Con A-induced response was not. The results suggest that RXM is a slight immunosuppressant to block the induction of IL-2 responsiveness by Df-stimulated patient's lymphocytes, resulting in the interruption of a cytokine cascade of allergic responses.
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All 16-membered macrolides showed very low MICs (MIC(50)s and MIC(90)s, < or =0.06-0.5 mg/L) for the erythromycin-susceptible isolates and for those with the M phenotype, but the telithromycin MICs for the M-type isolates were at least four times higher (MIC(90)s, 0.5 mg/L). In S. pyogenes, the MIC(50)s of 16-membered macrolides for the cMLS(B) isolates were > or = 256 mg/L, whereas that for telithromycin was 4 mg/L; the MIC(50)s of 16-membered macrolides and telithromycin ranged from < or = 0.06 to 0.5 mg/L for the iMLS(B) isolates with erm(A) and from 0.12 to > or = 256 mg/L for those with erm(B). In S. pneumoniae, the MIC(50)s of the 16-membered macrolides for the cMLS(B) isolates ranged from 0.5 to 128 mg/L, whereas for the iMLS(B) isolates their values ranged from < or = 0.06 to 4 mg/L; the MIC(50)s and MIC(90)s of telithromycin for both the cMLS(B) and the iMLS(B) isolates ranged from < or = 0.06 to 0.12 mg/L.
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To investigate the demethylated metabolites of roxithromycin (RXM) in humans and rats, and to study the antibiotic activity of these metabolites in vitro.
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Two independent reviewers identified studies and selected randomized trials and prospective cohort studies comparing the growth rate of AAA in patients with pharmacotherapy vs. no pharmacotherapy. We extracted information on study interventions, baseline characteristics, methodological quality, and AAA growth rate differences (in mm/year). Fourteen prospective studies met eligibility criteria. Five cohort studies raised the possibility of benefit of beta-blockers [pooled growth rate difference: -0.62 mm/year, (95%CI, -1.00 to -0.24)], but this was not confirmed in three beta-blocker RCTs [pooled RCT growth rate difference: -0.05 mm/year (-0.16 to 0.05)]. Statins have been evaluated in two cohort studies that yield a pooled growth rate difference of -2.97 (-5.83 to -0.11). Doxycycline and roxithromycin have been evaluated in two RCTs that suggest possible benefit [pooled RCT growth rate difference: -1.32 mm/year (-2.89 to 0.25)]. Studies assessing NSAIDs, diuretics, calcium channel blockers and ACE inhibitors, meanwhile, did not find statistically significant differences.
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While M. catarrhalis strains from children of the Kalgoorlie region were susceptible to many of the antibiotics used to treat respiratory tract infections, a large proportion of strains were resistant to ampicillin and/or co-trimoxazole. Current therapeutic guidelines, which recommend amoxicillin for treatment of otitis media, may need to be revised.
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A reliable and sensitive procedure is presented for the analysis of erythromycin (ERY) and oleandomycin (OLE) in food of animal origin, such as meat, liver, kidney, raw milk and egg. The method is based on a solid-phase extraction clean-up with a cation exchange cartridge, a 9-fluoromethylchloroformate (FMOC) precolumn derivatization and a separation by HPLC with fluorometric detection. The selectivity is satisfactory enough to control ERY and OLE residues as not many interfering peaks are observed for various food matrices. The macrolides recoveries of the total procedure were low, although >50%. However, addition of an internal standard (roxithromycin) corrected for recovery to give satisfactory quantitative results for repeatability, linearity, detection and quantification limits and mainly accuracy.
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To examine the effect of a 14-membered ring macrolide on airway mucus hypersecretion in rats treated with LPS.
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Dermatologists must be aware of the adverse effects of antimicrobial agents as well as various drug interactions that may influence the choice of drug as well as specific drug schedules. The development of modern antibacterials has improved the treatment of cutaneous bacterial infections. Macrolide antibacterials continue to be an important therapeutic class of drugs with established efficacy in a variety of skin infections. All macrolides inhibit protein synthesis by reversibly binding to the 23S ribosomal RNA in the 50S-subunit. Erythromycin, the prototype of macrolide antibacterials, was isolated from the metabolic products of a strain of Streptomyces erytherus in 1952. Originally, erythromycin was introduced as an alternative to penicillin because of its activity against the Gram-positive organisms. Numerous studies have demonstrated the efficacy and safety of erythromycin for various infectious diseases. Unfortunately, erythromycin is associated with a number of drawbacks including a narrow spectrum of activity, unfavorable pharmacokinetic properties, poor gastrointestinal tolerability, and a significant number of drug-drug interactions. Newer macrolides have been developed to address these limitations. The pharmacokinetics of azithromycin and clarithromycin allow for shorter dosing schedules because of prolonged tissue levels. The efficacy of azithromycin for the treatment of skin and soft tissue infections in adults and children is well established. The unique pharmakinetics of azithromycin makes it a suitable agent for the treatment of acne. Clarithromycin represents a clear advance in the macrolide management of patients with leprosy and skin infections with atypical mycobacteria. Dirithromycin and roxithromycin display no clinical or bacteriological adcantage over erythromycin despite a superior pharmacokinetic profile. An area of concern is the increasing macrolide resistance that is being reported with some of the common pathogens which may limit the clinical usefulness of this class of antimicrobial agents in future.
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A literature search using Medline was conducted from 1966 onwards, searching for articles with relevant key words such as macrolide, diffuse panbronchiolitis, community-acquired pneumonia, biofilm, immunomodulation, cystic fibrosis, erythromycin, clarithromycin, roxithromycin and azithromycin, bronchiectasis and asthma. When appropriate, additional references were found from the bibliographies of identified papers of interest. Any relevant scientific conference proceedings or medical texts were checked when necessary.
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Ranitidine two times 300 mg and roxithromycin two times 300 mg daily for 12 days, together with metronidazole three times 500 mg daily for the first ten days. To achieve final healing of the ulcer, treatment was then continued for a further 16 days with 300 mg ranitidine nocte.
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Proliferative response, cytokine production, and expression of mRNA of T cells stimulated with anti-CD3 and anti-CD28 mAbs in the presence or absence of monocytes, cytokine production of monocytes stimulated with lipopolysaccharide, and transendothelial migration of T cells in various concentrations of 5-I were analyzed. The effect of 5-I treatment was also evaluated in a mouse model of collagen-induced arthritis.
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Zhidan Huayu oral liquid could assist Rexithromycin to alleviate the condition of mice with MP, its mechanism may be related with the effect of reducing thrombosis and improving microcirculation.
Macrolide antibiotics are believed to inhibit mucus secretion but the mechanism of action is unclear. This study was designed to investigate an effect of roxithromycin on MUC2 gene expression in cultured intestinal epithelial cells (HM3-MUC2 cells). A reporter gene assay was used for analysis. Roxithromycin suppressed MUC2 gene transcriptional activity in a dose-dependent manner in HM3-MUC2 cells. Phorbol 12-myristate 13-acetate (PMA), lipoteichoic acid (LTA), lipopolysaccharide (LPS) and leukotriene D4 (LTD4) significantly increased MUC2 luciferase activities in the following order: PMA > LTA > LTD4 > LPS. Roxithromycin also decreased MUC2 gene transcriptional activity induced by PMA in a dose-dependent manner. NF-kappaB activation, but not AP-1 activation, was significantly suppressed by roxithromycin in HM3-MUC2 cells. A suppression of NF-kappaB activation was also observed in NCI-H292 cells. These results suggest that roxithromycin suppresses MUC2 gene expression in epithelial cells and that this suppression is probably via inhibition of NF-kappaB activation.
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The in vitro activity of tetracycline, doxycycline, erythromycin, roxithromycin, clarithromycin, azithromycin, levofloxacin and moxifloxacin was tested against 63 clinical isolates of Ureaplasma urealyticum. The minimal inhibitory concentrations (MICs) and the minimal bactericidal concentrations (MBCs) were determined by the broth microdilution method in A7 medium. The MIC(50) and MIC(90) of the tested agents after 24 h of incubation were as follows: tetracycline, 0.5 and 2.0 μg/ml; doxycycline, 0.125 and 0.25 μg/ml; erythromycin, 2.0 and 8.0 μg/ml; roxithromycin, 2.0 and 4.0 μg/ml; clarithromycin, 0.25 and 1.0 μg/ml; azithromycin, 2.0 and 4.0 μg/ml; levofloxacin, 1.0 and 2.0 μg/ml; and moxifloxacin, 0.5 and 0.5 μg/ml, respectively. The MIC values after 24 h and 48 h incubation differed by no more than one dilution for all the agents with the exception of doxycycline (two dilution difference for MIC(90)). Overall, moxifloxacin was the most active agent in vitro against U. urealyticum, with the narrowest difference between MIC and MBC values, followed closely by levofloxacin. Clarithromycin was the most active macrolide.
A novel universal aerosol-based detector Nano Quantity Analyte Detector--NQAD, connected with an ultra-performance liquid chromatography system is described. The detector was employed for detection of selected antibiotic compounds--macrolides (oleandomycin, erythromycin, troleandomycin, clarithromycin and roxithromycin) that are hard to detect using classical UV detectors due to the lack of chromophores. The determined lowest detection limits under isocratic conditions for these compounds ranged from 3.0 to 5.4 microg/mL. The suitability of the detector connected with ultra high-performance liquid chromatography in the gradient mode was tested on a more complex mixture containing 12 antibiotics. The detector exhibited full compatibility under both the elution modes when UHPLC separations were achieved in relatively short run times.
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To observe the effects of combined treatment with sansanmycin and macrolides on Pseudomonas aeruginosa and formation of biofilm.
Occasional superinfection or co-infection with Staphylococcus aureus led us to search for S. aureus carriage prospectively in patients with non-necrotizing bacterial dermophypodermitis, in particular erysipelas.
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Whether or not resistance to macrolide-lincosamide-streptogramin type B antibiotics (MLS) can be induced by many macrolide antibiotics (Mac), was inquired in Bacillus licheniformis EMR. Resistance to MLS in the strain was induced by erythromycin, oleandomycin, clarithromycin, roxithromycin, narbomycin, picromycin, kujimycin A or B, mycinamicin I, or rosamicin. On the contrary, josamycin, spiramycin, tylosin, rokitamycin, midecamycin, and miokamycin as well as lincosamide and streptogramin type B antibiotics could not induce MLS-resistance. The results suggest that two common chemical residues of the inducer Mac, that is, 1) a single monosaccharide at C5 in the 14- and 16-membered lactone rings, and 2) one polar group such as dimethylamino or methoxyl at C3' in the sugar, are likely to be responsible for showing the activity of MLS-resistance inducer in Bacillus licheniformis EMR.
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Roxithromycin, CAM, AZM, and INN significantly reduced the infarct volume in the high-dose group after 24 and 72 hours of reperfusion. All of the agents significantly decreased the edema in the high-dose groups at 24 and 72 hours, while only CAM and AZM significantly reduced the edema volume in the low-dose groups at 24 hours. All of the macrolide antibiotics at the high dose significantly improved neurological deficit scores at 24 and 72 hours. There were no differences in the CBF between the vehicle and respective antibiotic groups. In the experiment examining the interval, the 24-hour interval group exhibited the strongest neuroprotective effect.
Susceptibility pattern and resistance phenotype were determined by disk diffusion method and double disk test. Minimal inhibitory concentrations of antibiotics were obtained by the agar dilution method and evaluated according to the recommendations of the 'Comité de l'Antibiogramme de la Société Française de Microbiologie' (CA-SFM). The major determinants of erythromycin resistance in S. pyogenes (ermB, ermTR and mefA genes) were investigated by specific amplification protocols.
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In two ear, nose and throat (ENT) divisions, 74 patients affected by acute sinusitis of bacterial origin were selected and, after randomization in two balanced groups following an open parallel group design, assigned to treatment with brodimorprim and roxithromycin. At the beginning, after 3 days, 7 days and at the end of treatment the following symptoms were evaluated, using a four-step score: intensity of facial pain, headache, nasal stiffness, hyposmia, nasal secretion. The mean treatment period was 8.7 days. Tolerability was evaluated through registration and analysis of side effects and laboratory blood tests. The comparison between groups showed a better activity of brodimoprim on facial pain, headache, nasal stiffness and nasal secretion. The presence of resistant bacterial strains was greater in the group treated with roxithromycin (30.8%) when compared with the brodimoprim group (12.5%). Side effects were reported in 5 patients treated with brodimoprim and in 3 patients in the control group. Lab tests did not show serious variations.
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Genital chlamydia is the most commonly reported bacterial sexually transmitted infection (STI) in developed countries. In women, infection occurs most commonly between the ages of 16 and 19 years.
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Mastitis is one of the largest production concerns in the dairy industry worldwide. Mastitis caused by Staphylococcus aureus is a major concern to the dairy industry because of its resistance to antibiotic treatment. In this report, the results of antibiotic susceptibility test, carried out on 236 Staphylococcus aureus isolated from milk samples which were collected from cases of mastitis in cow herds of China, are presented. The regions and number of isolates include Inner Mongolia (112), Hebei (58) and Heilongjiang (66). Susceptibility to ampicillin, penicillin G, amoxicillin, piperacillin, cephalexin, cephazolin, cefotaxime, ceftazidime, cefoxitin, SMZ-TMP, gentamycin, kanamycin, norfloxacin, ciprofloxacin, ofloxacin, furaxone, torlamician, roxithromycin, clindamycin and vancomycin was determined by the disc diffusion method. Antibiotic susceptibility testing showed 87.30% (206 of 236) isolates were resistant to penicillin G. This result compares with the reports from other countries; the overall level of resistance was generally high for all antimicrobial agents tested.
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A surveillance study which is a part of the international surveillance on pneumococci resistance to penicillin and other antimicrobial agents was conducted in Beijing, China. More than 900 pediatric patients with respiratory tract infections aged from six months to three years selected from two pediatric units were enrolled in the study. Perthroat swabs were immediately streaked onto blood agar plates. Isolates were identified as pneumococci by their typical appearance, gram stain, confirmation tests. Antibiotic susceptibility was assessed by the disk diffusion method and minimal inhibition concentration (MIC) determination according to Protocol and National Committee for Clinical Laboratory Standards (NCCLS).
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In the present paper, the effect of roxithromycin on delayed-type hypersensitivity (DTH) was evaluated. Roxithromycin had no effect on sheep red blood cells (SRBC)-induced food pad swelling when orally administered in induction phase, whereas it suppressed the SRBC-induced DTH reaction and 2,4,6-Trinitrochlorobenzene (TNCB)-induced contact hypersensitivity (CHS) significantly when administered to mice in effector phase. For the sustained-CHS model induced by multi-challenge with TNCB, roxithromycin also inhibited the ear swelling when exposed to mice in three effector phases while showed no inhibitory effect on CHS by continuous treatment. Administration of this antibiotic in effector phase also down-regulated the MMP-9 activity and the higher in vitro survival of splenocytes from SRBC-challenged mice. Furthermore, this drug inhibited the gene expression of T-helper type 1 (Th1) cytokines such as IL-2 and IFN-gamma of lymph node cells from mice immuned by TNCB or of Con A-stimulated spleen cells. In addition, roxithromycin administered in vivo decreased the concanavalin A (Con A)-induced splenocyte proliferation without affecting the cell survival in vitro. These results suggest that roxithromycin might alleviate DTH reaction at least by suppressing the function and survival of effector T cells.
Ureaplasma urealyticum is considered as one of the main pathogens found in women with urogenital infection. This study aimed to investigate the relationship between the biovars, serovars, and their antimicrobial resistance against antibiotics in female patients with urogenital infection.
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The effects of various macrolide antibiotics [triacetyloleandomycin (TAO), clarithromycin, azithromycin, roxithromycin, erythromycin base] and the new ketolide HMR3004 on CYP3A expression were evaluated in human and rat hepatocytes. Cells were treated for 3 days with nontoxic concentrations of the drugs, and CYP3A induction was assessed through midazolam hydroxylase activity and Western and Northern blot analyses. In rat hepatocytes, no induction of CYP3A1 expression was observed following exposure to macrolides, even to erythromycin base and TAO (well known in vivo CYP3A1 inducers), whereas dexamethasone and phenobarbital were confirmed to induce this enzyme. In contrast, treatment of fresh and thawed human hepatocytes with TAO, produced an increase of midazolam hydroxylation (4-fold over control). This result was in agreement with the high amount of CYP3A4 protein and mRNA revealed by Western and Northern blot analyses. Other tested macrolides had no induction effect on CYP3A expression. These results confirmed the interspecies variability of CYP3A regulation in hepatocytes and raised the question of its mechanism of induction by macrolides in human liver.
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To evaluate the therapeutic effect of Roxithromycin (RXM), we studied 56 chronic sinusitis patients with nasal polyps using computed tomography (CT) and electron microscopy in addition to conventional clinical assessment. The paranasal sinus of subjects was observed clinically before and after daily administration of RXM at 300 mg for 3 months all underwent allergy testing for possible complications of allergic rhinitis based on subjective symptoms and objective findings. Improvement after RXM treatment was seen in 50.3% based on subjective symptoms and 59.1% based on objective findings. Overall improvement was seen in 53.6%. In 41 cases (73.2%) of all patients with chronic sinusitis and complications of allergic rhinitis, no significant difference was seen between patients with and without complications (53.7% in those with complications and 53.3% in those without). In CT analysis the paranasal sinus in 51.8% of all posttreated patients showed obvious improvement. In electron microscopy in chronic sinusitis patients with complications of allergic rhinitis, pretreated ethmoidal sinus tissues showed high mucous epithelial cell apoptosis in addition to common histological lesions, while posttreatment patients showed only eosinophil apoptosis in the interstitium and no apoptotic epithelial cells. We divided ethmoidal sinus lesions in patients without complications into 3 types and evaluated them as follows: In type 1, pretreated ethmoidal sinus tissues showed plasma cell infiltration and posttreatment cell apoptosis. In type 2, pretreated tissues showed lymphocyte and plasma cell infiltration and posttreated showed only some lymphocytes and no plasma cells. In type 3, proliferation of fibroblasts, most of which showed apoptosis, was seen in addition to apoptotic epithelial cells before treatment, while after treatment, these lesions remained with some apoptotic bodies phagocytosed by macrophages. In type 3 patients relapsed after surgery. Our findings indicate that RXM treatment had a significant therapeutic effect on chronic sinusitis with nasal polyps with and without complications of allergic rhinitis. We clarify the morphological mechanism of therapeutic effect of RXM on each type of ethmoidal sinus lesion divided by light and electron microscopy.