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The hemoglobinemia S is a genetic defect due to a replacement of a single amino acid in the beta-chain of the human hemoglobin, leading to the most characteristic case of primary blood hyperviscosity. The difference in beta-chain of normal HbA compared to that of HbS is represented by the replacement of glutamic acid, normally found in the 6th position, with valine. The sickling of HbS-containing erythrocytes is due to the polymerization of deoxygenated HbS tetramers with formation of linear structures and to the parallel distribution of these fibers in the red blood cell. The full deoxygenation of HbS blood induces the characteristic morphological changes of red blood cell and increases the blood viscosity from 40 to 120% if compared to the viscosity of the same oxygenated blood. Any change in the viscosity of normal blood following deoxygenation was observed. Almost all the clinical symptoms found in patients carrying HbS can be directly or indirectly correlated to the increased blood viscosity following deoxygenation.

A user programmable microcomputer-based integrated system for automatic analysis in the clinical chemistry laboratory is presented. Friendly user-instrument interaction helps the operator when defining tests and analytical conditions or entering sample data and test requests. Quality control data are retained for the automatic production of various statistical lists and graphs. Routine operator intervention is limited to reagent preparation, sample loading onto the autosampler plate, definition of the tests to be performed on each of the samples and data validation before the generation of reports. Finally, connection with an existing laboratory management system is provided by means of a standard serial interface.

Doxorubicin (Adr), daunorubicin (Dnr), and analogs of Adr modified in daunosamine (4'-epi-Adr and 3'-N-acetyl-Adr) were investigated with respect to their reaction with Fe(III) and analyzed for the ability of the corresponding iron complexes to sustain lipid peroxidation of isolated human platelet membranes. When the proportion of iron [25 microM Fe(III)] to Adr was 1:4, almost 50% of the metal was reduced following 1 hour of anaerobic reaction, while only approximately equal to 14% of the bound iron could be extracted as Fe(II) in the reactions of the Dnr complexes. The reaction of Adr was associated with formation of two main novel anthracyclines. One of the products had lost the C14 atom of the C9 chain and displayed chromatographic features and visible UV light spectra identical to those of authentic 9-dehydroxyacetyl-9-carboxyl-Adr. In complexes of iron and Dnr, no significant anthracycline degradation was observed. Reduction of anthracycline-bound Fe(III) by 4'-epi-Adr (38%) and 3'-N-acetyl-Adr (21.2%) was consistently less than that by Adr. Complexes of the anthracyclines investigated had different abilities to sustain lipid peroxidation, which was blocked (a) by the iron chelators deferoxamine and bathophenanthroline, indicating that Fe(III) and Fe(II) were needed for the reaction, and (b) by ICRF-198, the chelating product that forms intracellularly by hydrolysis of razoxane, which can prevent Adr cardiotoxicity. Peroxidation was not affected by scavengers of reduced oxygen radicals (superoxide dismutase, catalase, and mannitol). The isolated membranes contributed to the reduction of anthracycline-bound Fe(III) and probably represented the main determinant of lipid peroxidation by iron-Dnr. Lipid peroxidation was significantly less for complexes of iron with 4'-epi-Adr or 3'-N-acetyl-Adr than for complexes of iron with Adr. The observed differences may be relevant to the different biologic properties of Adr and its analogs, in particular their different degrees of cardiotoxicity.