Effects of methotrexate on the oxidative metabolism of cultured rabbit articular chondrocytes.

Objective: The mechanism of action of methotrexate (MTX) in inflammatory joint disease is still unclear. We examined the possible interactions of MTX with the oxidative metabolism of rabbit articular chondrocytes.

Methods: Cell cultures of articular chondrocytes enzymatically isolated from juvenile New Zealand white rabbits were incubated 24 h with either MTX (0.

Nebulized cyclosporine in the rat: assessment of regional lung and extrapulmonary deposition.

Background: Nebulized cyclosporine (CsA) has been shown to limit lung allograft rejection as well as intramuscular (IM) CsA, with limited blood diffusion. The present study determined the pharmacokinetic parameters of nebulized CsA, by the assessment of regional lung deposition and extrapulmonary diffusion of CsA.

Methods: CsA was given either by IM injection (10 mg/kg) or by aerosol (at 10 and 25 mg/kg doses); 70 rats were killed at 25 and 50 min, and at 2, 4, 6, 8, 12, 24, or 48 hr after CsA administration.

Pharmacodynamic activities of ciprofloxacin and sparfloxacin in a murine pneumococcal pneumonia model: relevance for drug efficacy.

We looked for associations between pharmacokinetic (Pk) and pharmacodynamic (Pd) parameters of ciprofloxacin (CPFX) and sparfloxacin (SPFX) and the in vivo efficacy of these antimicrobials in an immunocompetent mouse model of severe Streptococcus pneumoniae pneumonia. Bacterial killing curves recorded in the lungs during the 24 h after single subcutaneous injections of the fluoroquinolones (FQs) in doses ranging from 6.25 to 200 mg/kg were compared with mean Pk/Pd parameters in the serum of the same mice.

Use of a new mouse model of Acinetobacter baumannii pneumonia to evaluate the postantibiotic effect of imipenem.

Acinetobacter baumannii is responsible for severe nosocomial pneumonia. To evaluate new therapeutic regimens for infections due to multiresistant strains and to study the pharmacodynamic properties of various antibiotics, we developed an experimental mouse model of acute A. baumannii pneumonia.

Lack of correlation between hydrogen peroxide production and nitric oxide production by cultured rabbit articular chondrocytes treated with fluoroquinolone antimicrobial agents.

The arthrotoxicity of fluoroquinolone antibacterial agents so far remains unexplained. Recent experimental data have indicated an early stimulation of the oxidative metabolism within articular chondrocytes. An in vitro model was designed to analyse the production of oxygen-derived reactive species and glutathione by immature rabbit articular chondrocytes, and the influence of different fluoroquinolones on this model was examined.

Efficacy of single-dose ceftriaxone in experimental otitis media induced by penicillin- and cephalosporin-resistant Streptococcus pneumoniae.

We used a gerbil model of otitis media to assess the efficacy of single-dose ceftriaxone against three Streptococcus pneumoniae strains highly resistant to penicillin (MICs, 4 to 8 micrograms/ml) and with various susceptibilities to ceftriaxone (MICs, 0.5, 4, and 8 micrograms/ml). Middle ear infection was induced by bilateral transbullar challenge with 10(7) bacteria per ear.

Effect of subinhibitory concentrations of antimicrobial agents on adherence to silicone and hydrophobicity of coagulase-negative staphylococci.

OBJECTIVES: To study the effect of 0.25 MIC of antimicrobial agents on adherence to silicone and hydrophobicity of a slime-producing Staphylococcus epidermidis (ATCC 35984) and non-slime-producing Staphylococcus hominis (ATCC 35982). METHODS: Adherence was assessed in vitro, using silicone rubber immersed in a suspension of bacteria, pretreated with 0.

Mycobacterium avium complex infection in mice: lack of exacerbation after LP-BM5 murine leukemia virus infection.

The murine leukemia virus LP-BM5 has been used to reproduce the model of murine AIDS in order to evaluate the course of infection with the MO-1 strain of Mycobacterium avium complex (MAC). LP-BM5 was inoculated in C57BL/6 mice by intravenous (i.v.

[Effects of chloroquine on the replication of a murine retrovirus].

The wide use of chloroquine (Cq) for prophylaxis and chemotherapy of malaria in Africa, and the increased spread of AIDS in areas of this continent where malaria is endemic, raised the question of a possible interaction between chloroquine intake and HIV infection. Indeed, hydroxychloroquine and chloroquine itself have been shown to inhibit HIV-1 replication in vitro, hydroxychloroquine being proposed as a potential useful adjunctive therapy in the treatment of HIV-1 infection. On the other hand, chloroquine has been reported to enhance the replication of Semliki forest and encephalomyocarditis viruses in a mouse model.

Nebulized cyclosporine for prevention of acute pulmonary allograft rejection in the rat: pharmacokinetic and histologic study.

Background: With regard to limiting the systemic effects of cyclosporine A and obtaining better control of acute pulmonary allograft rejection, local immunosuppressive therapy with aerosolized cyclosporine A seems of interest. Given the in situ immunologic mechanisms of acute rejection, as well as the anatomic structure of the lung, this therapy is feasible as previously described by others. The aim of our study is to determine the pharmacokinetic parameters of nebulized cyclosporine A and the best modalities of administration.

Systemic prophylaxis of experimental staphylococcal endophthalmitis: comparative efficacy of sparfloxacin, pefloxacin, imipenem, vancomycin, and amikacin.

The preventive efficacy of several antibiotics in experimental staphylococcal endophthalmitis was evaluated. Two hours before bilateral intravitreal infection with 500 cfu of Staphylococcus aureus, 18 pigmented phakic rabbits were assigned to receive a single intramuscular injection of sparfloxacin (50 mg/kg), pefloxacin (50 mg/kg), imipenem (50 mg/kg), vancomycin (30 mg/kg), amikacin (15 mg/kg), or saline and were killed 24 h after infection (6 eyes/group). Sparfloxacin, pefloxacin, and imipenem were significantly (P < .

Evaluation of high-dose regimen of paromomycin against cryptosporidiosis in the dexamethasone-treated rat model.

In the dexamethasone-treated rat model of cryptosporidiosis, paromomycin was effective at a dosage of 50 mg/kg/day or more for ileal infection and 200 mg/kg/day or more for cecal infection. At 1 and 3 weeks after treatment, a persistent infection was demonstrated in all rats. These results confirm the anticryptosporidial activity of paromomycin and underscore the limitations of this compound because of its potential toxicity at such high dosages and its inability to eradicate the infection.

[The particular case of azalides: antibiotic diapedesis. Experimental data from a murine model of pneumococcal pneumonia].

The relations between the clinical efficacy, phagocytic transport phenomena, tissular and sera kinetics have been assessed in a pneumonia murine model. At first, the correlation between the clinical efficacy and pharmacokinetics characteristics has been studied for the erythromycin, spiramycin, roxithromycin, clarithromycin and azithromycin. An in vivo clinical efficacy hierarchy has been established (azi > ery > roxi = azi > spira).

Activities of roxithromycin against Mycobacterium avium infections in human macrophages and C57BL/6 mice.

The activity of roxithromycin against three clinical isolates of Mycobacterium avium was compared with that of clarithromycin both in a model of infection of human monocyte-derived macrophages and in a model of established infection of C57BL/6 mice. In the cell culture model, roxithromycin and clarithromycin were bactericidal for strains MO-1 and N-92159 and bacteriostatic for strain N-93043. For the three strains, the differences between the intracellular activities of roxithromycin and clarithromycin were not singificant after 7 days of treatment.

Tolerability, kinetics, and efficacy of subconjunctival pefloxacin in pigmented rabbits.

Pefloxacin has been shown to have good intraocular penetration when given systemically. In order to extend its clinical use, we have assessed the tolerability, kinetics, and efficacy of subconjunctival pefloxacin in phakic pigmented rabbits. The tolerability of a single subconjunctival injection of pefloxacin (0.

Use of normal C57BL/6 mice with established Mycobacterium avium infections as an alternative model for evaluation of antibiotic activity.

Several murine models have been used to evaluate the activities of antimicrobial agents against Mycobacterium avium infection. The main model used is the beige mouse model, but beige mice are expensive and not easily available. Thus, we developed a model of infection in wild C57BL/6 mice.

Effects of fluoroquinolones on cultured articular chondrocytes flow cytometric analysis of free radical production.

Using flow cytometry, we previously established in an ex vivo model that fluoroquinolones induce a stimulation of the oxidative metabolism in immature chondrocytes. To assess these findings in an in vitro model, primary cultures of immature articular chondrocytes were incubated with four quinolone solutions: ofloxacin, ciprofloxacin, nalidixic acid at 10 micrograms/ml for 24 hr and pefloxacin at 1, 10 and 100 micrograms/ml for various periods of time (2, 4, 6, 12, 24 and 48 hr). Three fluorochromes were used: DCFH-DA, reflecting cellular production of H2O2, rhodamine 123 (Rh123) and 10-N-nonyl-acridine orange (NAO), which are specific for mitochondrial activity and mass, respectively.

Interactions between murine AIDS (MAIDS) and toxoplasmosis in co-infected mice.

We coinfected C57B1/6 mice with LP-BM5 murine leukaemia viruses, responsible for murine AIDS (MAIDS), and an avirulent strain of Toxoplasma gondii. Virus-infected mice were infected perorally on day 30 with 10 cysts of T. gondii, and T.

Experimental evaluation of combined prophylaxis against murine pneumocystosis and toxoplasmosis.

Prophylactic efficacy of antimicrobial agents against pneumocystosis and toxoplasmosis was examined in a model of concurrent Pneumocystis carinii and Toxoplasma gondii infections in rats. Corticosteroid-treated rats naturally infected by P. carinii were challenged with the RH strain of T.

Otogenic meningoencephalitis induced by Streptococcus pneumoniae in gerbils.

Objective: Study and development of a gerbil model of pneumococcal meningoencephalitis secondary to acute middle ear (ME) otitis. Preliminary data raised the hypothesis of a direct bacterial dissemination from the ME focus to the central nervous system. This infection pattern was examined.

In vivo efficacy of a broad-spectrum cephalosporin, ceftriaxone, against penicillin-susceptible and -resistant strains of Streptococcus pneumoniae in a mouse pneumonia model.

The increasing emergence of penicillin-resistant (Pr) strains of Streptococcus pneumoniae could pose a therapeutic problem in the next few years. Ceftriaxone (CRO), a broad-spectrum cephalosporin, exhibits a smaller increase in MICs against Pr S. pneumoniae strains than amoxicillin (AMO) (usually referred as to the "gold standard" therapy for pneumococcal infections).

Chloroquine does not enhance the activity of clarithromycin against multiplication of Mycobacterium avium within human macrophages.

Setting: Chloroquine, an alkalinizing lysosomotropic agent, enhances the intracellular activity of antibiotics against Mycobacterium tuberculosis or Coxiella burnetii.

Objective: To determine if chloroquine modifies the activity of clarithromycin, less effective at acidic pH, against intracellular Mycobacterium avium.

Design: The activity of clarithromycin (4 micrograms/ml) against the MO-1 strain of M.