Glyco-optimization of aminoglycosides: new aminoglycosides as novel anti-infective agents

Glyco-optimization (OPopS) of aminoglycosides has been performed by replacing the existing sugar moiety with a variety of sugar derivatives. Glycosylation of the 6-position of nebramine provided a library of novel 4,6-linked aminoglycosides (AMGs). Among them, compounds 8b,g,i,l, and 8u with 2"-amino, 2",3"-diamino, 2",4"-diamino, 3",4"-diamino, 3"-amino groups, respectively, showed significant antimicrobial activity against Gram-(+) and -(-) bacteria. Several were particularly potent against Pseudomonus aeruginosa with MICs in the 1-2 microg/mL range.     

Pharmacokinetic monitoring during aminoglycosides: optimal therapy method of individual amikacin dosing]

One of the most successful approaches to adjustment of dosage regimens on the basis of single determinations of drug contents in blood specimens provides the blood sampling at the "ideal" moment (t*), i. e. at the time equal to the inverse value of the elimination rate constant. The above version of the one-point method is applicable to drugs obeying the one-compartment model. In practice, however, it is never known a priori whether the individual pharmacokinetic profile (PKP) is monoexponential or not. An attempt was made to apply the one-point method to individual amikacin (Am) intravenous bolus dosing in 27 patients with PKPs described not only by mono- but also by biexponential equations. The individual doses (Dc) estimated on the basis of Am concentrations recorded at the "ideal", point (2.75 hours after the administration) by the equation Dc = Dp.Cp(t*)/Ci(t*) were compared to the doses (DCl) found on the basis of greater than or equal to 4 determinations of the Am concentration (within 0.5 to 6 hours after the administration), i. e. by the equation DCl = Dp.Cli/Clp, where: Dp is the population value of an Am dose (7.5 mg/kg); Cp (t*) is the population value of an Am concentration at t* (6.7 mg/l), Clp is that of the total clearance [81.2 ml/(h.kg)] and Ci (t*) and Cli are the individual values of an Am concentration and clearance, respectively. The correlation coefficient of the DCl vs. Dc estimates was equal to 0.87. In 17 patients with monoexponential PKPs it was higher (r = 0.99).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effective use of regional intensive therapy units.

OBJECTIVE--To determine the effectiveness of regional intensive therapy units. DESIGN--Retrospective and prospective study of patients transferred to a regional intensive therapy unit over four years. SETTING--Glasgow regional intensive therapy unit. MAIN OUTCOME MEASURES--Severity of illness was assessed at the time of referral to the unit with the acute physiological and chronic health evaluation (APACHE) scoring system. Mortality was calculated. RESULTS--A significant association was found between increasing duration of illness before transfer and mortality, which was independent of the severity of illness. Mortality also varied depending on the referring hospital. CONCLUSIONS--When transfer of critically ill patients is required this should be done as early as possible to make best use of the services available. The mortality of patients transferred after 10 days casts doubt on whether further aggressive intensive therapy is appropriate.     

Mechanism of bactericidal action of aminoglycosides

[This corrects the article on p. 341 in vol. 51.].     

Action of aminoglycosides on platelet aggregation in vitro

The authors tested the influence of gentamicin, spectinomycin dihydrostreptomycin on the ADP and epinephrine in vitro induced platelet aggregation. Our aim was to demonstrate if platelet aggregation in vitro had some influences by antibiotics. A reduction in platelet aggregability, strictly dependent from the used antibiotic dose was observed. We have studied platelet function thanks to Born's method, adding to PRP gradual therapeutics doses of antibiotics. The results showed a reduction of platelet function which was dose-depended, and, particularly, gentamicin seemed to be the most effective among aminoglycosides. An interference between these drugs and the ADP and epinephrine binding to specific platelet receptor sites is proposed.     

Problems and solutions in myoblast transfer therapy

Duchenne muscular dystrophy is a severe X-linked neuromuscular disease that affects approximately 1/3500 live male births in every human population, and is caused by a mutation in the gene that encodes the muscle protein dystrophin. The characterization and cloning of the dystrophin gene in 1987 was a major breakthrough and it was considered that simple replacement of the dystrophin gene would ameliorate the severe and progressive skeletal muscle wasting characteristic of Duchenne muscular dystrophy. After 20 years, attempts at replacing the dystrophin gene either experimentally or clinically have met with little success, but there have been many significant advances in understanding the factors that limit the delivery of a normal dystrophin gene into dystrophic host muscle. This review addresses the host immune response and donor myoblast changes underlying some of the major problems associated with myoblast-mediated dystrophin replacement, presents potential solutions, and outlines other novel therapeutic approaches.     

Biogas purification process using intensive microalgae cultures

Summary The main contaminants (CO₂ and H₂S) in biogas produced by anaerobic digestion can be removed by an intensive mass culture of microalgae.