[Health care financing models]. / Modele finansowania opieki zdrowotnej.

The functioning of health care depends mainly on the level and method of financing. Countries choose between different models. Bismarck's model is financing based mainly on the contributions that are obligatory for employers and employees, decentralized model of managing and contracting services. Beveridge's model is financed mostly from the government taxes, it allows contributing to the cost of benefits for patients and participation by private sector. Residual model is based on the optional and private health insurances, supplemented only by National Health Service. Siemaszko's model in his assumption is based on the financing of benefits by the state budget, provides permanent control of the state and equal access to all the benefits for citizens. Choice of a specific financing model entails certain impact on all of the system's participants. The purpose of this article is to introduce subject of health care financing based on the literature and the authors' own thoughts.

Neuroprotective effects of tempol acyl esters against retinal ganglion cell death in a rat partial optic nerve crush model.

PURPOSE: The aim of this study is to search for more effective derivatives of the superoxide dismutase mimetic tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl). Although tempol is neuroprotective in a rat partial optic nerve crush (PONC) model, relatively high doses are required to exert this effect. METHODS: Tempol acyl esters with different-length fatty acids (tempol-C4, tempol-C8, tempol-C12 and tempol-C16) were synthesized and the following properties were evaluated: water-octanol partition coefficient, liposome-liposome energy transfer, and electron paramagnetic resonance (EPR). Brown Norway rats underwent PONC and received tempol or acyl esters intraperitoneally once daily for 7 consecutive days. We then compared the effects of tempol and its four esters on retinal ganglion cell (RGC) damage using a retrograde labelling method. RESULTS: The water-octanol partition coefficient increased with increasing length of attached acyl chain. However, the energy of the liposome-liposome transfer seemed to be optimal for tempol-C8 and tempol-C12. The EPR signal was very similar for all tested compounds, suggesting similar efficiency of superoxide scavenging. Partial optic nerve crush in vehicle-treated animals reduced RGC numbers by approx. 59% when compared with sham-operated eyes. Tempol did not affect RGC loss at a dose of 1 mg/kg. In contrast, at molar doses equivalent to 1 mg/kg of tempol, tempol-C8 showed a significant neuroprotective effect, whereas tempol-C4, tempol-C12 and tempol-C16 did not act neuroprotectively. CONCLUSION: Manipulating the hydrophobicity of tempol seems to be a promising tool for developing more potent neuroprotectants in the PONC degeneration model. However, the resulting compounds need further pharmacological evaluation.

Albumin adsorption on unmodified and sulfonated polystyrene surfaces, in relation to cell-substratum adhesion.

Albumin is commonly applied for blocking the adsorption of other proteins and to prevent the nonspecific adhesion of cells to diverse artificial substrata. Here we address the question of how effective these albumin properties are--by investigating unmodified and sulfonated polystyrene substrata with distinctly different wettabilities. As clearly shown with (125)I-radioisotopic assays, above a concentration of 10-20 µg/mL, the efficiency of bovine serum albumin (BSA) adsorption became markedly higher on the sulfonated surface than on the unmodified one. This study was assisted with the atomic force microscopy. On the unmodified surface, BSA, adsorbed from sufficiently concentrated solutions, formed a monolayer, with occasional intrusions of multilayered patches. Conversely, the arrangement of BSA on the sulfonated surface was chaotic; the height of individual molecules was lower than on the unmodified polystyrene. Importantly, the adhesion study of LNCaP and DU145 cells indicated that both surfaces, subjected to the prior BSA adsorption, did not completely loose their cell-adhesive properties. However, the level of adhesion and the pattern of F-actin organization in adhering cells have shown that cells interacted with unmodified and sulfonated surfaces differently, depending on the arrangement of adsorbed albumin. These results suggest the presence of some bare substratum area accessible for cells after the albumin adsorption to both types of investigated surfaces.

Atomic force microscopy evidence for conformational changes of fibronectin adsorbed on unmodified and sulfonated polystyrene surfaces.

The effect of polystyrene surface polarity on the conformation of adsorbed fibronectin (FN) has been studied with atomic force microscopy. We demonstrated that bare sulfonated and nonsulfonated polystyrene surfaces featured similar topographies. After the FN adsorption, direct comparison of both types of substrata revealed drastically different topographies, roughness values, and also cell-adhesive properties. This was interpreted in terms of FN conformational changes induced by the surface polarity. At high-solute FN concentrations the multilayer FN adsorption took place resulting, for the sulfonated substratum, in an increase of surface roughness, whereas for the nonsulfonated one the roughness was approximately stable. Conversely, the FN conformation characteristic for the first saturative layer tended to be conserved in the consecutive layers, as evidenced by height histograms. The height of individual FN molecules indicated, consonantly with the derived thickness of the adsorbed protein layer (the latter value being 1.4 nm and 0.6 nm, respectively, for an unmodified and sulfonated polystyrene surface), that molecules are flattened on polar surfaces and more compact on nonsulfonated ones. It was also demonstrated that the FN adsorption and conformation on polymeric substrata, and hence the resultant cell-adhesive properties, depended on the chemistry of the original surface rather than on its topography. Our results also demonstrated the ability of surface polarity to influence the protein conformation and its associated biological activity.

Semiquantitative evaluation of fibronectin adsorption on unmodified and sulfonated polystyrene, as related to cell adhesion.

The process of human fibronectin (FN) adsorption on nonsulfonated and sulfonated polystyrene surfaces was studied in relation to mechanisms of L1210 cell adhesion. Radioisotope assays directed towards FN, as well as ELISA measurements of adsorbed FN and bovine serum albumin (BSA) were carried out. (125)I radioisotope assays led to linear FN adsorption isotherms. When combined to ELISA measurements for FN, they revealed the multilayer adsorption. Results indicated a large difference in the saturating first-layer surface density of FN adsorbed on sulfonated and nonsulfonated polystyrene surfaces: significantly (ca. factor of 5) less FN molecules are necessary to complete a monolayer on sulfonated than on nonsulfonated polystyrene. This suggests an unfolded conformation of FN on sulfonated polystyrene, and a more compact one on the nonsulfonated polymer. Significant conformational changes of FN are also indicated by the following: (1) early phase of cell adhesion to FN adsorbed on sulfonated polystyrene surfaces is significantly (ca. factor of 6) higher than to FN on nonsulfonated surfaces, and in the former case adhesion proceeds mostly via alpha(5)beta(1) integrins; (2) RGD, the crucial fragment within central cell binding domain, seems to be partially hidden in the protein structure adopted on nonsulfonated surfaces; (3) patterns of F-actin organization differ in cells adhering to FN on sulfonated and nonsulfonated surfaces. The ELISA study directed against BSA (this protein always present on the surface after the adsorption of FN), showed the importance of "free area," uncovered by both proteins, which influence the cell adhesion processes.

Synthesis of optically active trans 4-cyclohexyl-L-proline as an intermediate product in the preparation of fosinopril.

A nine-step synthesis of trans 4-cyclohexyl-L-proline has been developed on a laboratory scale. The product is an intermediate in the preparation of fosinopril--an effective hypotensive drug. The total yield of the synthesis was 25%. The final product was 99.7% pure. Analytical methods were developed for each step of the synthesis (HPLC, TLC, IR, 1H-NMR, 13C-NMR, GC-MS, [alpha]D).

Formation of protoporphyrin IX from carboxylic- and amino-derivatives of 5-aminolevulinic acid.

BACKGROUND: Stability of ALA is an important factor for photodynamic therapy (PDT). The dimerization of ALA to pyrazines takes place via the amine group. It is, therefore, to be expected that blocking this group by addition of a formyl group should result in a more stable compound. METHODS: The ability of a new N-formyl derivative of ALA (N-f-ALA) to form protoporphyrin IX (PPIX) was compared with that of ALA and three of its ester (methyl, butyl and hexyl) derivatives. Dark toxicity of the compounds was measured using MTT assay. Formation of PPIX was measured by fluorescence spectroscopy. RESULTS AND CONCLUSIONS: N-f-ALA showed an outstanding stability in water solutions even at pH 7. However, it induced no PPIX neither in WiDr cells in vitro, nor in mouse skin in vivo. A probable reason is lack of an enzyme that can cleave the bond between the formyl group and ALA. Thus, steric hindrance may prevent processing of the compound into porphobilinogen. N-f-ALA did not inhibit PpIX formation from ALA and is unable to enter the heme cycle. Generation of ALA from its derivatives, therefore, seems to be an essential step in PPIX synthesis.

Fibronectin adsorption and arrangement on copolymer surfaces and their significance in cell adhesion.

The adsorption of fibronectin (FN) to (styrene/methyl methacrylate) copolymer surfaces, both sulfonated (hydrophilic) and nonsulfonated (hydrophobic), was studied by means of the radioisotope (125I-FN) and ELISA assays; the latter employed monoclonal antibodies. It was found that the radioiodination-derived isotherms did not follow the Langmuir-type adsorption law within the FN concentration range studied; rather, a quasi-linear FN surface density versus bulk concentration dependence was observed. These isotherms, and our recent ELISA measurements with polyclonal antibodies, allowed us to estimate saturative FN surface densities, which were, within the experimental error, similar on both types of surfaces. This suggested the amount of adsorbed FN to be not responsible for observed differences in leukaemia L1210 cell adhesion (FN-coated sulfonated surfaces are far more pro-adhesive than their nonsulfonated analogues). The presumption that these differences are induced by changes in the FN arrangement was confirmed by the use of monoclonal antibodies directed against distinct FN domains, and by the blocking of alpha5beta1 integrin receptor with the synthetic Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) peptide. The RGD sequence located within the FN cell-binding domain seems to be masked in the structure adopted on nonsulfonated surfaces, which hinders the integrin-ligand interaction.

The stability of 5-aminolevulinic acid and its ester derivatives.

Application of 5-aminolevulinic acid (ALA) and its esters for treatment of cancer and other disorders became a rapidly developing branch of photodynamic diagnosis and therapy. For clinical use, solutions of ALA (must be buffered to physiological pH. Unfortunately, in such conditions they are unstable. Two molecules of ALA condense and 2.5-(beta-carboxyethyl)-dihydropyrazine and 2.5-(beta-carboxyethyl)-pyrazine are formed. Although, numerous eleborations relate to stability of ALA alone very little or none is known about the stability of ester derivatives of ALA. The present investigations have comprised the stability of ALA and its esters at 37 degrees C in respect of pH. concentration and time of reaction. The studies showed that ALA esters alike ALA undergo dimerisation at pH near 5. Moreover, it is possible that at pH>5.5 hydrolysis of the esters occurs, but this elaboration do not comprise explanation of this phenomenon.

The synthesis and applications of 5-aminolevulinic acid (ALA) derivatives in photodynamic therapy and photodiagnosis.

A route has been developed to high-purity precursors, viz., ALA esters, to be used in photodiagnosis and photodynamic therapy. Hexyl, butyl and methyl 5-aminolevulinates are similar to the ALA acid in chemical stability and efficacy in producing the appropriate photosensitizer PpIX. Tests carried out on animal models showed the method based on the esters to be the more selective.

Microwave-assisted synthesis of O'-adamantylated uracil-derived nucleosides.

Microwave-induced synthesis of O'-adamantyl derivatives of AZT, thymidine, 2'-deoxyuridine and uridine was investigated. Contrary to heterocyclus adamantylation of uracil and uridine in trifluoroacetic acid, the microwave-induced reaction provided sugar-substituted compounds.

Adsorption characteristics of human plasma fibronectin in relationship to cell adhesion.

Adsorption of human plasma fibronectin (FN) on nonsulfonated and sulfonated polymer surfaces was studied, by using a polyclonal antiserum to FN and the ELISA method. ELISA signal was recorded as a function of FN concentration in solutions. The concentration dependence of FN binding shows the saturation effect in the range 5-10 microg/mL. ELISA data are discussed in the terms of a self-assembled monolayer and different conformations of the FN molecule. The early adhesion of L1210 cells to polymer surfaces after prior adsorption of FN on these surfaces was studied under static conditions. In the case of FN adsorbed on sulfonated surfaces, the relative number of adhering cells increased with the increase of the interfacial surface tension (i.e., the cell adhesion depends on the surface density of sulfonic groups). However, in the case of FN adsorbed on nonsulfonated surfaces, the relative number of adhering cells was low and independent on the interfacial surface tension. The alpha(5)beta(1)-integrin blocking by a monoclonal antibody resulted in a strong inhibition of the cell adhesion to FN adsorbed on sulfonated polymer surfaces. This indicates that cell adhesion to FN adsorbed on these surfaces is mostly mediated by the alpha(5)beta(1)-integrin. In contrast, in the case of FN adsorbed on nonsulfonated surfaces the cell adhesion was not inhibited by the alpha(5)beta(1)-integrin blocking.