The inducement of K+ permeability through membranes by the polyene antibiotic amphotericin B (AmB) has been analyzed as a measure of the antibiotic activity. Dose-response curves have been obtained with cholesterol- and ergosterol-containing egg yolk phosphatidylcholine large unilamellar vesicles (LUVs), human erythrocytes, and Saccharomyces cerevisiae cells. Conductance changes induced by AmB in sterol-containing planar bilayer membranes have also been studied. AmB self-association in aqueous buffer was determined by circular dichroism (CD) as a function of the antibiotic concentration. Electronic absorption and CD spectra of AmB were recorded in the presence of LUVs. For given AmB concentrations, the extent of permeability inducement is dependent on the lipid concentration. On the other hand, for cholesterol-containing LUVs or erythrocytes, a critical AmB concentration had to be reached before any permeability is observed. Independent of lipid concentration, this concentration was directly related to antibiotic self-association in the aqueous buffer. The same observation was made for erythrocytes and nystatin. The AmB absorption and CD spectra were totally different for ergosterol- and cholesterol-containing LUVs. Formation of single channels by one-sided addition of AmB could be observed only in ergosterol-containing membranes. These data lead us to propose that the permeability pathways induced by amphotericin B or nystatin, in ergosterol- and in cholesterol-containing membranes, are of different natures. In the latter case the antibiotics are only active, by single-sided addition, in the self-associated form. These findings offer important clues for the design of less toxic derivatives of AmB: they should have a low degree of self-association in water.

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A b s t r a c tBackground: Poland represents a country of high cardiovascular (CV) risk. The association between lipid abnormalities and increased CV risk is well established. Therefore, it is important to monitor the prevalence and control of dyslipidaemia. Aim:To evaluate serum lipids concentrations as well as the prevalence, awareness, and control of lipid abnormalities in a representative sample of adults in Poland. Methods:In 2011, in a national cross-sectional survey blood samples were collected from 1168 males and 1245 females, aged 18-79 years, for measurement of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and triglycerides (TG) in blood serum. Low density lipoprotein cholesterol (LDL-C) was calculated using Friedewald's formula.Results: Mean serum TC concentration was 197.1 mg/dL in males (M) and 198.6 mg/dL (95% CI 195.7-201.5) in females (F). Levels of LDL-C were 123.6 mg/dL (120.9-126.2) and 123.7 mg/dL (121.4-126.1), HDL-C -45.8 mg/dL (44.7-47.0) and 54.1 mg/dL (53.1-55.1), TG -140.9 mg/dL (133.0-148.8) and 104.0 mg/dL (99.8-108.2) for males and females, respectively. TC ≥ 190 mg/dL was found in 54.3% subjects (M 54.3%; F 54.4%). After adding patients on lipid-lowering treatment, hypercholesterolaemia was present in 61.1% of adults (M 60.8%; F 61.3%). LDL-C ≥ 115 mg/dL was detected in 57.8% of all subjects (M 58.3%; F 57.3%), while HDL-C < 40 mg/dL in 35.2% of males and < 45 mg/dL in 22% of females TG ≥ 150 mg/dL was found in 21.1% of subjects (M 28.4%; F 14.0%). The highest prevalence of elevated TC and LDL-C levels was present in the age group of 40-59-year-olds. Of those with hypercholesterolaemia 58.7% (M 61.5%, F 56.0%) were not aware of the condition; 22.0% (M 21.0%, F 24.5%) were aware but were not being treated; 8.1% (M 7.7%, F 8.5%) were treated but with TC ≥ 190 mg/dL; and only 10.9% (M 10.7%, F 11.0%) were being treated with TC < 190 mg/dL. Conclusions:The prevalence of dyslipidaemia in Poland continues to be high -over 60% of adults have hypercholesterolaemia, and control remains poor. The results of the NATPOL 2011 survey call for urgent preventive measures.

In Poland there are still nearly 20 million individuals with hypercholesterolaemia, most of them are unaware of their condition; that is also why only ca. 5% of patients with familial hypercholesterolaemia have been diagnosed; that is why other rare cholesterol metabolism disorders are so rarely diagnosed in Poland. Let us hope that these guidelines, being an effect of work of experts representing 6 main scientific societies, as well as the network of PoLA lipid centers being a part of the EAS lipid centers, certification of lipidologists by PoLA, or the growing number of centers for rare diseases, with a network planned by the Ministry of Health, improvements in coordinated care for patients after myocardial infarction (KOS-Zawał), reimbursement of innovative agents, as well as introduction in Poland of an effective primary prevention program, will make improvement in relation to these unmet needs in diagnostics and treatment of lipid disorders possible.

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With the consent of Authors and Editorial Boards of respective journals, the Guidelines are published in parallel in Diagnostyka Laboratoryjna (PSLD recommendation) and Archives of Medical Science (PoLA recommendation).

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