Uptake and intracellular activity of an optically active ofloxacin isomer in human neutrophils and tissue culture cells

The penetration of an optically active ofloxacin isomer [(-)-ofloxacin] into human neutrophils and different tissue culture cells (HEp-2, McCoy, MDCK, and Vero) was studied and compared with that of ofloxacin by a fluorometric assay. The cellular-to-extracellular-concentration ratios (C/E) of (-)-ofloxacin were always higher than 6, significantly greater than those of ofloxacin at extracellular concentrations of 5 and 10 mg/liter. The penetration of (-)-ofloxacin and ofloxacin was doubled when neutrophils were stimulated by phorbol myristate acetate but not affected after ingestion of opsonized Staphylococcus aureus. The C/E ratios of (-)-ofloxacin and ofloxacin for different tissue culture epithelial cells and fibroblasts were lower than those of neutrophils but still higher than 2. Both compounds produced a significant reduction in viable intraphagocytic S. aureus during 3 h of exposure to antimicrobial agents. We conclude that (-)-ofloxacin appears to reach higher intracellular concentrations than ofloxacin, remaining active inside the neutrophils

Intracellular penetration and activity of BAY Y 3118 in human polymorphonuclear leukocytes

The penetration of a new quinolone (BAY Y 3118) into human polymorphonuclear leukocytes (PMNs) was evaluated by a fluorometric assay. The cellular concentration-to-extracellular concentration (C/E) ratio was higher than 6.3 at extracellular concentrations ranging from 2 to 100 mg/liter. The uptake of BAY Y 3118 was rapid, reversible and nonsaturable. The intracellular penetration of BAY Y 3118 was significantly affected by environmental temperature (C/E ratio at 4°C, 5.4 ± 0.5; control, 7.5 ± 0.9; P < 0.05) and cell viability (C/E ratio in dead PMNs, 5.5 ± 0.8; control, 7.5 ± 0.9; P < 0.05), but it was not affected by metabolic inhibitors. The ingestion of opsonized zymosan or opsonized Staphylococcus aureus significantly decreased the levels of PMN-associated BAY Y 3118. Cell stimulation by a membrane activator, however, significantly increased the intracellular concentration of this quinolone. At therapeutic extracellular concentrations (0.5, 2, and 5 mg/liter), BAY Y 3118 showed intracellular activity greater than that of ciprofloxacin against S. aureus in human PMNs. It was concluded that BAY Y 3118 reaches high intracellular concentrations within human PMNs and remains active intracellularly

Intracellular penetration and activity of gemifloxacin in human polymorphonuclear leukocytes

The intracellular penetration and activity of gemifloxacin in human polymorphonuclear leukocytes (PMN) were evaluated. Gemifloxacin reached intracellular concentrations eight times higher than extracellular concentrations. The uptake was rapid, reversible, and nonsaturable and was affected by environmental temperature, cell viability, and membrane stimuli. At therapeutic extracellular concentrations, gemifloxacin showed intracellular activity against Staphylococcus aureus

Photodynamic Therapy Combined with Antibiotics or Antifungals against Microorganisms That Cause Skin and Soft Tissue Infections: A Planktonic and Biofilm Approach to Overcome Resistances

The present review covers combination approaches of antimicrobial photodynamic therapy (aPDT) plus antibiotics or antifungals to attack bacteria and fungi in vitro (both planktonic and biofilm forms) focused on those microorganisms that cause infections in skin and soft tissues. The combination can prevent failure in the fight against these microorganisms: antimicrobial drugs can increase the susceptibility of microorganisms to aPDT and prevent the possibility of regrowth of those that were not inactivated during the irradiation; meanwhile, aPDT is effective regardless of the resistance pattern of the strain and their use does not contribute to the selection of antimicrobial resistance. Additive or synergistic antimicrobial effects in vitro are evaluated and the best combinations are presented. The use of combined treatment of aPDT with antimicrobials could help overcome the difficulty of fighting high level of resistance microorganisms and, as it is a multi-target approach, it could make the selection of resistant microorganisms more difficult

Uptake and intracellular activity of moxifloxacin in human neutrophils and tissue-cultured epithelial cells

The penetration by moxifloxacin of human neutrophils (polymorphonuclear leukocytes [PMN]) and tissue-cultured epithelial cells (McCoy cells) was evaluated by a fluorometric assay. At extracellular concentrations of 5 mg/liter, the cellular-to-extracellular concentration ratios (C/E) of moxifloxacin in PMN and McCoy cells were 10.9 ± 1.0 and 8.7 ± 1.0, respectively (20 min; 37°C). The uptake of moxifloxacin by PMN was rapid, reversible, nonsaturable (at extracellular concentrations ranging from 1 to 50 μg/ml), and not affected by cell viability. The uptake of moxifloxacin was affected by external pH and the environmental temperature. The incubation of PMN in the presence of sodium fluoride, sodium cyanide, and carbonyl cyanide m-chlorophenylhydrazone significantly decreased the C/E of this agent. Neither PMN stimulation nor phagocytosis of opsonized Staphylococcus aureus significantly affected the uptake of moxifloxacin by human PMN. This agent, at concentrations of 0.5, 1, and 5 mg/liter, induced a significant reduction in the survival of intracellular S. aureus in human PMN. In summary, moxifloxacin reaches much higher intracellular concentrations within phagocytic and nonphagocytic cells than extracellular ones, remaining active inside the neutrophils

Uptake and intracellular activity of sparfloxacin in human polymorphonuclear leukocytes and tissue culture cells

The penetration of sparfloxacin into human neutrophils (PMN) and different tissue culture cells (HEp-2 and McCoy) was evaluated. The cellular to extracellular concentration ratios (C/E) of sparfloxacin were always higher than 4 at extracellular concentrations ranging from 0.5 to 25 mg/liter. The uptake of sparfloxacin by PMN was rapid, nonsaturable, reversible, not energy dependent, and significantly reduced at pH 8. The penetration of this agent into PMN was similar when viable and Formalin-killed cells were used and was not affected by environmental temperature. Ingestion of opsonized zymosan significantly increased the amount of PMN-associated sparfloxacin. Sparfloxacin at a concentration of 0.5 mg induced a significant reduction in the survival of intracellular Staphylococcus aureus. It is concluded that sparfloxacin reaches intracellular concentrations within leukocytic cells much higher than extracellular concentrations, while remaining active intracellularly

Uptake and intracellular activity of fluconazole in human polymorphonuclear leukocytes

The penetration of fluconazole into human polymorphonuclear leukocytes (PMNs) and tissue culture epithelial cells (McCoy) was evaluated. At different extracellular concentrations (0.5 to 10 mg/liter), fluconazole reached cell-associated concentrations greater than the extracellular ones in either human PMNs (intracellular concentration to extracellular concentration ratio, ≥2.2) or McCoy cells (intracellular concentration to extracellular concentration ratio, ≥1.3). The uptake of fluconazole by PMNs was rapid and reversible but was not energy dependent. The intracellular penetration of fluconazole was not affected by environmental pH or temperature. Ingestion of opsonized zymosan and opsonized Candida albicans did not significantly increase the amount of PMN-associated fluconazole. At therapeutic extracellular concentrations, the intracellular activity of fluconazole against C. albicans in PMNs was significantly lower than that of amphotericin B. It was concluded that fluconazole reaches high intracellular concentrations within PMNs but shows moderate activity against intracellular C. albicans in vitro

De la opresión al bienestar. Explorando poder, opresión y bienestar entre inmigrantes marroquíes en España

Durante las últimas décadas, millones de personas han llegado a países de la Unión Europea para mejorar su calidad de vida y la de sus familiares. Las diferentes culturas, mercados y servicios que encuentran en Europa, fomentan en estos nuevos ciudadanos de la Unión Europea expectativas de satisfacción de sus necesidades, reconocimiento justo de sus aportaciones. Sin embargo, frecuentemente los inmigrantes se incorporan a un mercado laboral precario, que les obliga a asentarse en barrios sin acceso a servicios y recursos sociales, fomentando actitudes de rechazo en los vecinos nativos. La incorporación de los inmigrantes se realiza, por tanto, en condiciones asimétricas, que dificultan sus posibilidades para desarrollar su proyecto migratorio. En este contexto, la adaptación de la comunidad inmigrante se configura como uno de los principales desafíos para el presente y futuro de la Unión Europea