Pharmacogenomics of phase II metabolizing enzymes and drug transporters: clinical implications.

The clinical impact of pharmacogenomics remains a hot topic of current research efforts. Although pharmacogenomics of phase I metabolizing enzymes seems to have been well studied, knowledge on the clinical impact of genetic variability of phase II metabolizing enzymes and drug transporters is more limited. This paper reviews data on the pharmacogenomics of phase II metabolizing enzymes as well as of ATP binding cassette transporters and of solute carrier transporters focusing on clinical implications for drug efficacy and drug toxicity. The clinical impact of some of these polymorphisms has been well defined i.e. the association between polymorphisms of organic anion transporter polypeptides and statin induced myopathy. However, as the same drug may be substrate for different enzymes and different transporters, it is difficult to elucidate the impact of each polymorphism. Investigating the impact of multiple polymorphisms might be more clinically meaningful, although methodologically challenging.

Protective effect of salicylates against hydrogen peroxide stress in yeast.

AIMS: To investigate the effects of salicylates in Saccharomyces cerevisiae exposed to oxidative stress induced by hydrogen peroxide (H(2)O(2)). METHODS AND RESULTS: Saccharomyces cerevisiae was cultured through to the postlogarithmic phase of growth. Stress was induced by the addition of 1.5 mmol l(-1) H(2)O(2) for 1 h, while N-acetyl-l-cysteine (NAC) and glutathione (GSSG) were used as control agents that affect the redox balance. Sodium salicylate, at 0.01-10 mmol l(-1)or acetylsalicylic acid, at 0.02-2.5 mmol l(-1) was administered at various times before hydrogen peroxide stress. Both agents conferred resistance to a subsequent hydrogen peroxide stress, similarly to the induction of the adaptive response observed upon pretreatment with NAC and GSSG. Sodium salicylate was more potent as a short-term, but not as a long-term pretreatment agent, compared to acetylsalicylic acid. CONCLUSIONS: Pharmacological pretreatment with salicylates resulted in dose related increases in cell survival, indicating the induction of the protective response in yeast. SIGNIFICANCE AND IMPACT OF THE STUDY: The possible role of salicylates in the modulation of the hydrogen peroxide stress response in eukaryotic cells address questions on the effects of these commonly used therapeutic agents in a number of disorders exhibiting an oxidative stress component.

Adherence to guidelines for antibiotic prophylaxis in general surgery: a critical appraisal.

OBJECTIVES: To evaluate the adherence of general surgeons to guidelines for antimicrobial prophylaxis. This study was held from January 2000 until October 2000 in a General Surgery Clinic in a hospital in Athens, Greece. METHODS: Eight hundred and ninety-eight patients were enrolled and operated on electively. Questionnaires concerning demographic data, health status, type of surgery (clean and clean-contaminated) and parameters of antibiotic prophylaxis (antibiotic choice, route, dose, timing of first dose, timing of operative redosing and duration of prophylaxis) were completed. RESULTS: Of the patients, 44.8% underwent a clean surgical operation and 55.2% underwent a clean-contaminated surgical operation. Inguinal hernia repair and laparoscopic cholecystectomy were the commonest operations in each category. Second-generation cephalosporins were the most frequently prescribed antibiotics, in 67%. Although, only 78.5% of procedures required prophylaxis, it was administered in 97.5%, so it was not justified and inappropriately administered in 19%. It was revealed that 100% of patients received antibiotic prophylaxis on time. The choice of antimicrobial agent was appropriate in 70% and the duration of prophylaxis was optimal in 36.3%. The overall compliance rate of surgeons with guidelines for antibiotic prophylaxis was 36.3%. CONCLUSIONS: Adherence to separate aspects of guidelines for surgical prophylaxis has to be improved. The duration of antibiotic prophylaxis was the main parameter of interest. Interventions have to be made about the development, distribution and adoption of adequate guidelines in collaboration with surgeons.