Cationic liposomes/DNA complexes are widely used vectors for delivering genes in clinical and experimental trials. Relatively low transfer efficiencies in vivo compared with viral gene transfer may be improved using local application. In addition, markedly increased transfer efficiency may be achieved in vitro and in vivo via optimization of known variables influencing liposomal transfection. Lipofection under different conditions was performed in various cell lines and primary porcine smooth muscle cells. Optimized conditions found in vitro were verified in vivo using a porcine restenosis model. Toxicity was monitored analyzing cell metabolism. Transfer efficiency and safety were determined using morphometry, histology, galactosidase assays, PCR, and RT-PCR. The most important variables enabling maximum transfer efficiency were firstly the appropriate selection of cationic lipids for the cell type to be transfected, secondly the DNA/liposome ratio chosen, which depended on the cell type and cationic lipids used, and thirdly the state of proliferation of the targeted cells. Transfection in vivo demonstrated two- to fivefold higher transfer efficiencies when transfer conditions were extrapolated from optimization experiments in stationary cells compared with the use of conditions established in proliferating cells. Application of the therapeutic gene for cecropin using optimized transfer conditions resulted in a significantly reduced neointima formation compared with the transfection using a control gene for ss-galactosidase. Thus, in this vascular model, initial optimization of lipofection in stationary cells in culture followed by local delivery in vivo and with selection of a suitable therapeutic gene led to markedly improved transfer efficiencies, gene expression, and biological effect. Stationary cell cultures simulate more realistically the in vivo situation and may therefore represent a better model for future in vivo experiments. In addition, the advantages of liposomes are easy handling, low toxicity, and the lack of carcinogenicity or immunogenic reactions.

No abstract

Aim: This study evaluated the impact of hyperuricemia (HUR) on outcome in patients with different types of impaired renal function (IRF) and acute myocardial infarction (AMI) treated invasively. Methods: Out of 3,593 consecutive AMI patients treated invasively, 1,015 IRF patients were selected. The IRF group consisted of patients with baseline kidney dysfunction (BKD group) and/or patients with contrast-induced nephropathy (CIN group). HUR was defined as a serum uric acid concentration (SUAC) >420 µmol/l (>7 mg/dl). Independent predictors of death and major adverse cardiovascular events (MACE) were selected by the multivariate Cox-regression model. Results: Remote mortality rates were higher in HUR patients: IRF (32.7 vs. 18.6%), BKD (41.3 vs. 25.9%), CIN (35.4 vs. 16.7%); all p < 0.001. HUR was an independent predictor of death in BKD (hazard ratio (HR) 1.38, p < 0.05). Each 100-µmol/l increase in SUAC was associated with a significant increase of HR for mortality: 1.087 in IRF patients, 1.108 in BKD patients, 1.128 in CIN patients; all p < 0.05. Remote major adverse cardiovascular event rates were higher in HUR patients: IRF (55.4 vs. 48.9%), CIN (56.8 vs. 48%); both p < 0.05. Conclusions: In AMI patients treated invasively, an increase in SUAC is an independent predictor of death within all types of renal dysfunction; HUR defined as SUAC >420 µmol/l (>7 mg/dl) is a predictor only in BKD patients.

The aim of this study was to determine the prevalence rates of mucopolysaccharidoses in Poland and to compare them with other European countries. A retrospective epidemiological survey covering the period between 1970 and 2010 was implemented. Multiple ascertainment sources were used to identify affected patients. The overall prevalence of mucopolysaccharidoses in the Polish population was 1.81 per 100,000. Five different mucopolysaccharidoses were diagnosed in a total of 392 individuals. MPS III was the most frequent mucopolysaccharidosis, with a birth prevalence of 0.86 per 100,000 live births. A prevalence of approximately 0.22 cases per 100,000 births was obtained for MPS I. For MPS II, the prevalence was estimated as 0.45 cases per 100,000 births; for MPS IV A and B as 0.14 cases in 100,000 births; and that for MPS VI as 0.03 cases per 100,000 births. 1. The prevalence pattern of mucopolysaccharidosis in Poland is lower when compared to the prevalence reported for other European countries, such as the Netherlands, Czech Republic, or Germany, but similar to countries like Sweden and Denmark. 2. Different frequencies of the various forms of mucopolysaccharidosis were observed. 3. In the case of MPS VI, the incidence values for Poland were the lowest of all the studies previously published so far.

No abstract