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[The effect of finoptin on the accumulation of doxorubicin in leukemia P388 cells with induced resistance to the antibiotic].

Using male mice BDF1, it has been shown that the retention period of doxorubicin (DOX) is shorter in the leukemia P 388 cells with induced antibiotic resistance (P 388/DOX) as compared to the P 388 cells, sensitive to DOX. Administration of finoptin (FP) to animals leads to the increase of DOX concentration in the leukemia P 388/DOX cells during 240 min observation. FP promotes the therapeutic effect of DOX on mice bearing leukemia P 388/DOX. It can be suggested that the mechanism of FP action is the damaged DOX elimination from cells with induced resistance, since FP doesn't change the period of antibiotic circulation in the murine blood plasma.

Animals↗

The quinolones.

The molecular basis of activity, chemistry, microbiology, and pharmacology of the new fluoroquinolones is reviewed in this article. Areas of clinical use are analyzed with specific reference to efficacy, development of resistance, and potential for toxicity.

4-Quinolones↗

Abnormal regulation of IFN-alpha, -beta, and -gamma expression in MAIDS, a murine retrovirus-induced immunodeficiency syndrome.

Mice infected with LP-BM5 murine leukemia viruses (MuLV) develop a syndrome with many features in common with AIDS including lymphadenopathy and profound immunodeficiency associated with enhanced susceptibility to infection and terminal B cell lymphomas. To evaluate cellular defects that may predispose infected mice to these sequelae, we studied the regulation of IFN gene expression. Spleen cells from mice infected with LP-BM5 MuLV expressed high levels of IFN-gamma mRNA by 1 wk post-inoculation and throughout the course of disease. By comparison, transcripts of IFN-alpha/beta genes were not detected in spleen cells at any time after infection. In uninfected mice, expression of IFN-alpha/beta genes is induced rapidly after infection with New-castle disease virus, but mice inoculated with LP-BM5 MuLV were unable to induce these genes by 4 wk after retroviral infection. Inhibition of IFN-alpha/beta induction due to LP-BM5 MuLV infection also occurred in nude mice, indicating this effect was not mediated by activated T cells. Furthermore, low levels of IFN-gamma transcripts were detected in spleens of nude infected mice, suggesting that cells other than T cells can express this gene. These results suggest that the normal contributions of IFN to control of microbial spread, immune surveillance, and lymphoid interactions are disrupted by infection with LP-BM5 MuLV.

Animals↗

Microbiological properties of sulbactam combined with ampicillin.

Several in vitro parameters of sulbactam combined with ampicillin (Sbt/Amp) were studied in order to evaluate and compare its microbiological properties with those of beta-lactamase stable beta-lactams (ceftriaxone, cefamandole, cefoxitin). The intrinsic activity of Sbt/Amp was satisfactory and comparable to that of other beta-lactams and no significant difference was observed against beta-lactamase producing or non-producing bacteria. Besides, it was determined that sulbactam, when combined with ampicillin at different ratios (1:2, 5:1), with and without preincubation (60 min) reduces the hydrolysis of ampicillin determined by ten different standard beta-lactamases. The hydrolysis rates of ampicillin become as low as those of cefoxitin, cefamandole and ceftriaxone, which are beta-lactamase stable cephalosporins. In fact, all the antibiotics under examination were slightly hydrolyzed by several beta-lactamases, but such slight hydrolysis did not affect the antibacterial activity against beta-lactamase producing bacteria. About 50% of non-beta-lactamase producing bacteria (18 strains of different bacterial species) produced an inducible beta-lactamase after ten daily subcultures with sub-inhibitory concentrations of each antibiotic, but minimum inhibitory concentrations (MICs) of Sbt/Amp never increased after stimulation in contrast with other drugs whose MICs were much higher in consequence of this procedure. Finally, no spontaneous resistant mutant to Sbt/Amp was detected, but several mutants appeared in response to the other drugs. Sulbactam makes ampicillin as effective as beta-lactamase stable cephalosporins and its use does not determine an increase of resistance or selection of resistant mutants.

Ampicillin↗

In vitro influence of charcoal on ciprofloxacin activity.

The effect of charcoal-containing media on ciprofloxacin (BAY o 9867) has been evaluated. The minimal inhibitory concentrations of ciprofloxacin are increased by the presence of charcoal, thus a correction factor has to be calculated to know the real efficacy of the drug, especially in life-threatening infections such as pneumonia due to Legionella spp.

Charcoal↗

N-acetylcysteine and 2-mercaptoethane sulphonate inhibit anti-pseudomonas activity of antibiotics in vitro.

The in vitro activity against Pseudomonas aeruginosa was investigated for serial dilutions of eight anti-Pseudomonas antibiotics in combination with serial dilutions of N-acetylcysteine (NAC) and 2-mercaptoethane sulphonate (MES). The results indicated that addition of NAC and MES to the antibiotics increased the MIC values for tobramycin, netilmicin, piperacillin, azlocillin, cefsulodin, ceftazidime and imipenem but not for colistin. The decrease of MIC found in high concentrations of NAC and MES was probably due to the bacteriostatic effect of the drugs per se and not to synergism with the antibiotics.

Acetylcysteine↗

Pseudomonas aeruginosa and cystic fibrosis: unusual bacterial adaptation and pathogenesis.

Pseudomonas aeruginosa is an adaptable, saprophytic bacterium with the potential to cause a variety of opportunistic infections in compromised hosts. In patients with cystic fibrosis, chronic pulmonary colonization with mucoid alginate-producing mutants of P. aeruginosa is a major cause of morbidity and mortality and is an interesting example of microbial adaptation and host-bacterium interaction.

Adaptation, Physiological↗

[Ciprofloxacin in combination with other antimicrobial substances].

The antibacterial activity of ciprofloxacin, either alone or in combination with azlocillin, imipenem, mezlocillin or tobramycin, was tested against enterococcus and pseudomonas species. No synergy or antagonism was found by means of the checkerboard titration method used. Subsequently, the bactericidal activity of ciprofloxacin (2 x minimal inhibitory concentration, MIC), azlocillin, imipenem, mezlocillin or tobramycin (2 x MIC) either alone or in combination (1 x MIC each of each substance) was tested against individual strains. No reduction of bactericidal activity in comparison with the effect of the single substances at higher concentration was found, even though the concentrations of each substance were halved. An antagonism is unlikely when ciprofloxacin is combined with one of the beta-lactams studied or with tobramycin. More likely is a slight synergistic effect.

Anti-Bacterial Agents↗

Antimicrobial spectrum, pharmacology and therapeutic use of antibiotics. Part 1: tetracyclines.

The mode of action, bacterial resistance, in vitro activity, pharmacology, dosage, adverse reactions, interactions and indications for tetracyclines are reviewed. Suggestions for the selection of a particular tetracycline are provided. It is concluded that there is only one pertinent difference among the tetracyclines, namely, that doxycycline, and probably minocycline, can be given in full dosage and with minimal risk to patients with renal impairment.

Bacteria↗

Serum bactericidal activity against Klebsiella pneumoniae in volunteers receiving increasing doses of tobramycin with or without cefamandole.

Ten volunteers received intravenously in a randomly allocated order and on separate days the following regimens: cefamandole (15 mg/kg); tobramycin (1.5 mg/kg); tobramycin (3 mg/kg); cefamandole (15 mg/kg) + tobramycin (1.5 mg/kg); cefamandole (15 mg/kg) + tobramycin (3 mg-kg). Tobramycin serum levels were 3.7 +/- 0.7 micrograms/ml one hour after infusion of the 1.5-mg/kg and 7.8 +/- 1.6 micrograms/ml after the higher dose. Cefamandole serum levels were 26.0 +/- 5.2 micrograms/ml at the same time. Serum bactericidal activity and killing-rate studies were performed on a collection of 18 strains of Klebsiella pneumoniae. Against cefamandole-sensitive strains, all regimens were satisfactory (median serum bactericidal activity 1:16 to 1:64). Tobramycin (3 mg/kg) and both combinations were slightly more active on cefamandole-resistant strains (1:16 to 1:32) than cefamandole (1:2) and tobramycin low dose (1:8). Except for cefamandole alone, all regimens were equivalent in killing studies.

Adult↗

Drug therapy reviews: Antimicrobial spectrum, pharmacology and therapeutic use of antibiotics--part 4: aminoglycosides.

The aminoglycoside antibiotics are reviewed with regard to mechanism of action, bacterial resistance, antimicrobial spectrum, combinations with other agents, pharmacology, dosages in patients with normal and impaired renal function, adverse reactions, therapeutic use, prophylatic use and selection. Streptomycin is suggested in the therapy of tuberculosis, brucellosis, tularemia and yersinia infections; several of these require the coadministration of another agent. The choice between streptomycin and gentamicin for combination therapy of enterococcal endocarditis may be simplified by knowledge of the prevalence of high-level streptomycin-resistant strains in the hospital or by use of an in vitro screening test. Neomycin is the agent used orally in the treatment of hepatic encephalopathy. Paromomycin is indicated only for the treatment of amebic infections. The major difference among gentamicin, tobramycin and amikacin lies in the low but increasing prevalence of gram-negative bacilli which are resistant to gentamicin and tobramycin and susceptible to amikacin. In those institutions in which gentamicin-resistant strains are of concern, amikacin is the aminoglycoside of choice in high-risk patients until the infecting bacterium has been determined.

Aminoglycosides↗