Biomedical subjects
Publications and source records attributed to A Georgopoulos.
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The in vitro antibacterial activity of fosfomycin was compared to that of oxacillin, cefazolin, ceftriaxone and vancomycin against isolates of Staphylococcus aureus from patients treated at the University of Vienna General Hospital. Of 211 strains, 104 were methicillin-susceptible and 107 were methicillin-resistant. Fosfomycin inhibited over 90% of the strains at concentrations of less than or equal to 64 mg/l, independent of methicillin susceptibility or resistance. The minimal bactericidal concentrations (MBC) were one dilution above the minimal inhibitory concentrations (MIC). Vancomycin showed activity similar to fosfomycin while other beta-lactam antibiotics such as oxacillin, cefazolin and ceftriaxone were inactive against methicillin-resistant S. aureus. Fosfomycin at a high dosage seems to be a potential drug for the treatment of infections due to methicillin-resistant S. aureus.
A persistent suppression of bacterial growth following limited exposure to an antimicrobial agent, the postantibiotic effect (PAE), has been described for a variety of antibiotics and microorganisms. In this study the PAE of ceftriaxone and gentamicin was determined in vitro on three strains each of Klebsiella pneumoniae, Pseudomonas aeruginosa and Streptococcus viridans. The strains were exposed to the substances for 2 h at varying concentrations. Ceftriaxone was used at the minimal inhibitory concentration (MIC) and 1/2 MIC and gentamicin at 1/2 MIC, 1/4 MIC, and 1/8 MIC, each alone and in combination. Antibiotic concentrations were reduced by 1,000-fold dilution, bacterial regrowth was consequently monitored by viable count. The PAE of ceftriaxone alone reached up to 145 min (MIC) and 50 min (1/2 MIC), that of gentamicin alone up to 170 min (1/2 MIC), 135 min (1/4 MIC) and 70 min (1/8 MIC), depending on the bacterial species. Combinations of the antibiotics produced longer PAEs than one substance alone; the longest PAE was produced by the combination of ceftriaxone (MIC) and gentamicin (1/2 MIC) lasting up to 320 min (S. viridans). It may be important to take the PAE into account when evaluating dosing intervals.
In vitro beta-lactam antibiotics like ceftriaxone and penicillin G sodium have been shown to be active against Borrelia burgdorferi. Results of quantitative determinations of both antibiotic substances in the CSF for children are limited. Seventy-five children (median age 96 months, range 10 to 176 months) with probable or definite neuroborreliosis were treated with ceftriaxone (1 x 50-90 mg/kg/day) or penicillin G sodium (4 x 80,000-120,000 IU/kg/day) intravenously. On day 10 of therapy levels of penicillin G sodium (1,1.5,2,3,4, 5, or 6 h after i.v. administration), and ceftriaxone (1,2,4,6,12 or 24 h after i.v. administration) in serum and CSF were measured with a micro agar diffusion bioassay. Results demonstrate that after 5 h penicillin G sodium in CSF was above the minimal inhibitory concentration (MIC) but after 6 h penicillin G sodium levels were below the determination limit in 60% of the cases. All ceftriaxone results in CSF-even after 24 h-were above MIC. Penicillin G sodium serum values ranged from 46.6 to 0.1 mg/L (1 to 6 h post dose) and ceftriaxone serum values from 261 to 5 mg/l (1 to 24 h post dose). The role of penicillin G sodium and ceftriaxone and administration intervals of both antibiotics in the therapy of neuroborreliosis in children are discussed.
Tumor necrosis factor alpha (TNF alpha) and interleukin 6 (IL6) are cytokines with a varied spectrum of inflammatory and immunological activities, for example modulation of acute phase proteins, fever and stimulation of B-lymphocytes. Mycobacterium avium has been shown to stimulate the release of TNF alpha and IL6 from cultured human monocytes and macrophages into the cell supernatant. Cultured human monocytes were infected with Mycobacterium kansasii and M. avium. The concentrations of TNF alpha and IL6 were measured in the supernatant. Monocytes infected with M. kansasii produced significantly lower amounts of TNF alpha (34.8 +/- 20.3 pg/ml) and IL6 (12.0 +/- 8.9 pg/ml) compared to monocytes infected with M. avium (198.3 +/- 171.7 pg/ml and 63.2 +/- 37.6 pg/ml respectively). The extent of cytokine production might be relevant for the clinical manifestation of mycobacterial disease.
In an in vitro study 246 clinical isolates of erythromycin-resistant staphylococci from six hospitals in Austria were investigated for susceptibility to josamycin and other, newer macrolide antibiotics, e.g. roxithromycin and clarithromycin. 71 strains of Staphylococcus aureus showed an MIC > or = 4 mg/l and 100 strains of S. aureus showed an MIC > or = 256 mg/l. In addition, 25 strains of coagulase-negative staphylococci resistant to erythromycin at an MIC of > or = 4 mg/l were investigated. At an MIC of 2 mg/l 57% of the erythromycin-resistant strains of S. aureus were inhibited by josamycin, 25% by clarithromycin and 11.6% by roxithromycin. At an MIC of 2 mg/l 13.3% of erythromycin-resistant coagulase-negative staphylococci were inhibited by josamycin, 10.7% by clarithromycin and 9.3% by roxithromycin. This study suggests that josamycin is still active in vitro against more than 50% of erythromycin-resistant strains of S. aureus. This drug is also more active than roxithromycin and clarithromycin against erythromycin-resistant S. aureus.
The pharmacokinetic parameters of mitoxantrone in patients with liver metastasis after intra-arterial 2 h and 24 h infusion (dosage 12 mg/m2) were investigated. Peak plasma concentrations were 305 +/- 60 ng/ml at 2 h infusion and 244 +/- 89 ng/ml at 24 h infusion. These peak plasma concentrations occurred at 0.9 +/- 0.8 h during 2 h infusion and 5.5 +/- 3.4 h during 24 h infusion. No significant difference between both intra-arterial administrations in elimination half-life (50-223 h at 2 h infusion, 58-246 h at 24 h infusion) and area under the plasma concentration-time curve (AUC0-72 = 11.6 micrograms/ml.h for 2 h infusion, AUC0-72 = 11.2 micrograms/ml.h for 24 h infusion) could be found. The results indicate that no change of availability in the central compartment at infusion of mitoxantrone over a period of 24 h could be achieved. The 2 h infusion lead to sufficient plasma levels with pharmacokinetic parameters of mitoxantrone similar to 24 h infusion and showed a good clinical picture with mild toxicity.
To assess the effect of simvastatin on fasting and postprandial triglyceride (TG)-rich lipoproteins in subjects with type 1 diabetes and elevated LDL cholesterol levels, eight patients participated in a simvastatin versus placebo, randomized, crossover study. At the end of each drug period fasting and postprandial lipoprotein studies were undertaken. Fasting plasma total and LDL cholesterol and apolipoprotein B (apo B) were significantly lower on simvastatin compared to placebo. Postprandial studies: simvastatin versus placebo consistently decreased the area under the curve (AUC, mean+/-SEM) of TG in plasma (12.52+/-9.07 versus 18.70+/-10.48 mmol x h/L, p = 0.02). Similarly, TG AUC was lower: in the chylomicron subfraction (Sf > 400) 3.24+/-2.71 versus 5.27+/-4.61 mmol x h/L p = 0.03; and in the [chylomicron remnant + VLDL] subfraction (Sf 20-400) 3.98+/-2.51 versus 7.04+/-3.88 mmol x h/L, p = 0.01. This was due to decreased particle n umber rather than size, as shown by a decrease in the AUC of apo B in Sf 20-400 (600+/-360 versus 980+/-600 mg x h/L, p = 0.02) and the lack of change in the ratio of TG/apo B. Intestinal lipoproteins contributed to the simvastatin effect, as shown by the lower AUC of retinyl esters in both subfractions. Chylomicrons: 627.61+/-363.43 versus 948.19+/-568.34 nmol x h/L, p = 0.02 and remnants: 129.23+/-67.12 versus 208.49+/-92.11 nmol x h/L, p = 0.04. Our data suggest an additional mechanism by which simvastatin can decrease the risk of atherosclerosis in patients with type I diabetes: a decrease of the number of circulating intestinal and hepatic postprandial TG-rich lipoprotein particles.
Liposomes prepared from lipids isolated from Triticum sp. (wheat germ) were used to investigate the percentage of Vinblastine encapsulation and its retention into liposomes. The wheat germ total lipids (TL) were extracted by the Bligh-Dyer method and the lipid classes have been isolated using chromatographic techniques. The type of lipids and their percentage content have been examined by TLC coupled with an FID (latroscan). Two liposomal formulations, i.e., I and II, with encapsulated vinblastine, and formulation III (empty liposomes) have been prepared by thin film hydration method. The cytotoxic/cytostatic activity of these liposomal formulations have been examined against nine human leukemic cell lines. The results showed that the percentage content of vinblastine into liposomes I and II depended on the lipid composition and it was greater into formulation II (> 90%). The retention of the drug into liposomes was studied and found to be time-dependent at 37 degrees C. For the cytotoxic/cytostatic activity, the parameters GI50, TGI, LC50 were estimated according to the instructions given by the NCI. The results show that formulation III (empty liposomes), exhibited a growth inhibiting activity, against the most tested cell lines. Formulation II showed mean of LC50 at 124.6 nM, mean of TGI at 71.6 nM and mean of GI50 at 30.8 nM.
Vinblastine was encapsulated into liposomes composed from lipids dimiristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC), with cholesterol and transfersomes with sodium cholate prepared by the thin film hydration method. The percentage of vinblastine encapsulation, the stability of transfersomes and liposomes and the rate of release of encapsulated vinblastine at 37 degrees C were studied. The results showed that encapsulation of vinblastine into liposomes was higher than 98% at a drug/phospholipid molar ratio from 0.17 to 0.18, while encapsulation of vinblastine into transfersomes varied from 50% to 80% at a drug/phospholipid molar ratio from 0.05 to 0.09. The retention of drug in liposomes and in transfersomes was found to be time/dependent. The retention of drug in transfersomes compared to the liposomes was reduced due to the presence of sodium cholate which caused destabilization and reduced the main phase transition temperature Tm of the PC bilayers. The cytotoxic/cytostatic activity of the two liposome formulations and the two transfersome formulations with or without encapsulated vinblastine were examined against nine human cell lines and the parameters GI50, TGI, LC50 were estimated according to the NCI protocol. Free DPPC/sodium cholate liposomes found to exhibit strong antiproliferative activity in contrast to the other three free liposomal formulations (DPPC/cholesterol, DMPC/cholesterol, DMPC/sodium cholate). On the other hand, vinblastine encapsulated into the liposomes found to exhibit 20-fold less activity on average, in the three parameters calculate compare to the free vinblastine.
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Explore the source record for details and available documents.