The effects of simvastatin and fenofibrate on malondialdehyde and reduced glutathione concentrations in the plasma, liver, and brain of normolipidaemic and hyperlipidaemic rats.

The objective of study was to investigate the effects of different doses of simvastatin and fenofibrate on malondialdehyde (MDA) and reduced glutathione (GSH) in the plasma, liver, and brain tissue of male normolipidaemic and hyperlipidaemic rats. Normolipidaemic (Wistar) rats were receiving 10 or 50 mg/kg a day of simvastatin or 30 or 50 mg/kg a day of fenofibrate. Hyperlipidaemic (Zucker) rats were receiving 50 mg/kg/day of simvastatin or 30 mg/kg/day of fenofibrate. Control normolipidaemic and hyperlipidaemic rats were receiving saline. Simvastatin, fenofibrate, and saline were administered by gavage for three weeks. In normolipidaemic rats simvastatin and fenofibrate showed similar and dose-independent effects on plasma and brain MDA and GSH concentrations. Generally, plasma and brain MDA decreased, while brain GSH concentration increased. In hyperlipidaemic rats simvastatin did not affect plasma and brain MDA and GSH concentrations but significantly decreased liver GSH. Fenofibrate decreased plasma and liver MDA but increased brain MDA. In both rat strains fenofibrate significantly decreased liver GSH concentrations, most likely because fenofibrate metabolites bind to GSH. Our findings suggest that simvastatin acts as an antioxidant only in normolipidaemic rats, whereas fenofibrate acts as an antioxidant in both rat strains.

Effects of simvastatin and fenofibrate on butyrylcholinesterase activity in the brain, plasma, and liver of normolipidemic and hyperlipidemic rats.

The study objective was to test the hypothesis that simvastatin and fenofibrate should cause an increase in butyrylcholinesterase (BuChE) activity not only in the plasma and liver but also in the brain of normolipidemic and hyperlipidemic rats. Catalytic enzyme activity was measured using acetylthiocholine (ATCh) and butyrylthiocholine (BTCh) as substrates. Normolipidemic and hyperlipidemic rats were divided in four groups receiving 50 mg/kg of simvastatin a day or 30 mg/kg of fenofibrate a day for three weeks and three control groups receiving saline. Simvastatin and fenofibrate caused an increase in brain BuChE activity in both normo- and hyperlipidemic rats regardless of the substrate. The increase with BTCh as substrate was significant and practically the same in normolipidemic and hyperlipidemic rats after simvastatin treatment (14-17% vs controls). Simvastatin and fenofibrate also increased liver and plasma BuChE activity in both normolipidemic and hyperlipidemic rats regardless of the substrate. In most cases the increase was significant. Considering the important role of BuChE in cholinergic transmission as well as its pharmacological function, it is necessary to continue investigations of the effects of lipid-lowering drugs on BuChE activity.

The association of uric acid with glucose and lipids in general population: Croatian cross-sectional study.

Hyperuricemia may have an important role in metabolic syndrome, cardiovascular diseases and stroke. Elevated serum uric acid concentration has been shown to be the strong predictor of cardiovascular mortality in several recently published studies. Our aim was to determine the prevalence of hyperuricemia in general Croatian population and to investigate the association of serum uric acid with glucose and lipids. This was a retrospective cross-sectional study on 6,476 consecutive adults. Prevalence of hyperuricemia was 13.9% in general population and it was significantly higher in males, than in females (26% vs. 6%; p < 0.001). Median uric acid concentration was higher in males than in females (343 vs. 238 micromol/L; p < 0.001). Age, glucose and lipid parameters did not correlate with uric acid. In hyperuricemic subjects, increased concentrations of glucose (33.1% vs. 13.1%; p < 0.001), triglycerides (46.9% vs. 17.6%; p < 0.001), total cholesterol (69.6% vs. 51.9%; p < 0.001), LDL-cholesterol (64.5% vs. 46.4%; p < 0.001) and decreased concentration of HDL-cholesterol (24.3% vs. 13.0%; p < 0.001) were more prevalent than in subjects with normal serum concentrations of uric acid. Hyperuricemia is highly prevalent in Croatian general population and it aggregates with hyperglycemia and dyslipidemia.

Antibiotic use optimization program in the largest Croatian university hospital--benefits of restrictions on unlimited antibiotic use.

The aim of this study was to obtain the relevant information on antibiotic use in a 750-bed Croatian university hospital. The study has been designed as a 2-point prevalence interventional analysis. For each patient on antibiotic therapy, diagnosis, indication for treatment, antibiotic therapy, dosage and route of administration together with the results of microbiological studies (if available) were obtained. After the first prevalence analysis in 2001, a restriction on unlimited antibiotic use was introduced. The second analysis, performed in 2002, after restrictions on antibiotic use, revealed reductions in the rates of restricted release antibiotics and overall antibiotic use with decreases from 38.6% to 36.9% and 23.4% to 23.2% respectively (p = 0.87). The first survey showed that the 5 most often prescribed antibiotics in the therapy of bacterial infections were: gentamicin, other aminoglycosides, carbapenems, amoxycillin +clavulanate and vancomycin with proportions of 14.8%, 10.3%, 8.2%, 7% and 7% respectively. In the year 2002, the most prescribed antimicrobial drugs in the therapy of bacterial infections were: gentamicin, quinolones, vancomycin, carbapenems and cefuroxime with proportions of 18.6%, 11.4%, 9.7%, 9.3% and 8% respectively. A reduction in the proportions of doubtful antibiotic therapy, from 24.6% before the intervention, to 24.2% after the restrictions, accompanied by a 0.4% rise in the rates of indicated antibiotic therapy was also observed (p = 0.93). Our study shows that restrictions on formerly unlimited use of antimicrobials, even when leading to an improvement in their prescribing, do not necessarily cause rapid and significant reduction in the overall use of antibiotics or explicit positive financial effects.

Use of gastroprotective agents in recommended doses in hospitalized patients receiving NSAIDs: a drug utilization study.

OBJECTIVE: In recent years, studies investigated to what extend recommendations for co-prescribing gastroprotective agents in prevention of NSAID-induced gastrointestinal complications are followed in clinical practice. However, only a few studies have also taken into consideration the recommended dose of gastroprotectives prescribed in NSAID-induced ulcer prophylaxis. The aim of our study was to evaluate the prevalence of concomitant use of gastroprotectives with NSAIDs in hospitalized patients, with emphasis on the recommended dose of gastroprotectives for ulcer prophylaxis. METHOD: This observational, cross-sectional, drug utilization study included all adult patients receiving NSAIDs hospitalized in the Clinical Hospital Center Zagreb on the day of the study. Data on age, sex, comorbidities, indications for NSAID use, type/dose of NSAIDs and gastroprotectives, history of gastrointestinal events, active gastrointestinal symptoms and risk factors were evaluated. MAIN OUTCOME MEASURE: Study outcomes were: (1) prevalence of prescription of gastroprotectives among NSAID-users at risk; (2) prevalence of prescription of gastroprotective in recommended dose; (3) association between risk factors and prescription of GPAs. RESULTS: The rates of gastroprotectives prescription were significantly higher in NSAID-users with concomitant risk factors as compared to patients without risk factors [47/70 (67.1%) and 8/22 (36.4%), respectively; p=0.01072]. However, gastroprotection in recommended ulcer-preventive dose was low in both groups [8/70 (11.4%) and 9/92 (9.8%), respectively]. The number of concomitant risk factors did not increase the odds of receiving anti-ulcer therapy (odds ratio 0.7279). Thirty-three percent of patients with concomitant risk factors were not prescribed gastroprotectives. Ibuprofen, NSAID with the lowest risk of inducing gastrointestinal complications, was prescribed in only two patients. CONCLUSION: The results indicate high awareness among hospital physicians about possible NSAID-induced gastrointestinal complications, but insufficient knowledge about risk factors related to NSAID-induced gastrointestinal toxicity, recommended dose of gastroprotectives in NSAID-induced ulcer prophylaxis and gastrointestinal toxicity of different types of NSAIDs.

[Oxycodone: a strong opioid in the treatment of patients with arthritis]. / Oksikodon: jaki opioid u lijecenju reumatskih bolesnika.

Reducing pain is a major goal in treating patients with arthritis. Oral controlled-release opioid products enable patients to better maintain pain control due to convenient dosing intervals and sustained blood concentration. Oxycodone is a strong opioid that has proved to be efficacious in analgesic studies of persistent moderate to severe pain in patients with degenerative and inflammatory rheumatic diseases. Beyond significant pain control and better physical function, controlled-release oxycodone improved coping with pain in patients with osteoarthritis.

[Evaluation of justification for antibiotic use at the Internal Medicine Clinic of the Clinical Hospital in Zagreb]. / Procjena opravdanosti potrosnje antibiotika u Klinici za unutrasnje bolesti Klinickog bolnickog centra Zagreb.

OBJECTIVE: Resistance to antimicrobials as the result of unnecessary and inadequate use of antibiotics has become a global health problem. It is estimated that up to 50% of antimicrobials are used unnecessarily, and that they are the cause of approximately 25% of adverse drug reactions. Efforts are made to ensure a controlled use of antibiotics, which is the key strategy against development of resistance to antimicrobials. Since antimicrobial drugs are among the most commonly prescribed drugs in hospitals, a rational use of antibiotics would also help reduce health care costs. There are limited data on the use of antibiotics in Croatian hospitals. METHODS: This observational study was conducted at the University Department of Medicine, Zagreb University Hospital Center, with the aim to investigate the prevalence of antimicrobial use, indications for antibiotic use, and the necessity and adequacy of antibiotic therapy. The investigated parameters were: prescribed antibiotic (dose, route of administration, duration of therapy), indication for use of antibiotics (prophylaxis, treatment), diagnosis, presence of positive culture, indication documented in medical records, evaluation of antibiotic therapy by a specialist, and risk factors. The most important parameter in the evaluation of the necessity of antimicrobial use was the presence of culture days of treatment, and indication for treatment documented in medical records and evaluated by a specialist. The data were collected over 1 day using a standardized questionnaire. RESULTS: Fifty of 138 (37%) hospitalized patients were receiving 1 or more antibiotics, most of them (80%) for the treatment of infection. The most frequent diagnoses were sepsis (64%), urinary tract infection (25%), abdominal infection (21%), and pulmonary infection (7%). The median therapy duration was 4 days (minimum 1 day, maximum 121 days). The most frequently prescribed antibiotics were fluoroquinolones (23%), penicillins (23%), aminoglycosides (18%) and cephalosporins (11%). Thirty-nine patients received one or more reserve antibiotics. The median number of received antibiotics was 2 (minimum 1, maximum 5 antibiotics). Risk factors were present in 76% of patients. Fifty-nine percent patients were receiving antibiotics on the basis of culture; in most of them therapy was evaluated by a specialist (98%) and the indication was documented in medical records. Reserve antibiotics were prescribed in 34 patients, in 77% of them on the basis of positive culture. CONCLUSION: The high prescription rate of antibiotics (fluoroquinolones), concomitant use of antibiotics of a similar spectrum of activity and lack of sequential therapy emerged to be the parameters needing further evaluation. Other investigated parameters (number of antibiotics, duration of therapy, necessity of antibiotic therapy) were in accordance with similar studies conducted in hospitals. Further investigation with emphasis on local problems and prescription habits with the aim to optimize the use of antibiotics is needed.

Acquired coagulopathy due to anticoagulant rodenticide poisoning.

A 35-year-old woman was admitted to hospital because of epistaxis, hematomas, and metrorrhagia. Laboratory data indicated severe coagulopathy with prolonged prothrombin time and decreased serum concentrations of vitamin K-dependent clotting factors II, VII, IX, and X. The patient denied taking any oral anticoagulants. She was given transfusions of red blood cells, fresh frozen plasma (1,180 mL) and phytomenadione daily for 6 weeks (total dose 550 mg), which normalized the coagulation factors concentration. After all other possible causes of acquired coagulopathy had been excluded, rodenticide poisoning was suspected on the basis of her epidemiologic history. The patient was a war refugee from Bosnia and Herzegovina. During her absence, the troops of United Nations Protection Force performed rodent extermination in and around her house. History data and therapeutic effects suggested that the coagulopathy had been caused by prolonged exposure to long-acting anticoagulant rodenticide. This could also explain the need for protracted phytomenadione therapy.