QSAR modeling and transmission electron microscopy stereology of altered mitochondrial ultrastructure of white blood cells in patients diagnosed as schizophrenic and treated with antipsychotic drugs.

Treatment of patients diagnosed as schizophrenic with antipsychotic drugs (neuroleptics) is known to cause occasional unexplained depletion of white blood cells, especially neutrophil granulocytes. It has been known for many years that neuroleptics can interfere with the mitochondrial respiratory chain in vitro. Because there has been a growing interest recently in mitochondrial targeting of drugs, and since a quantitative structure-activity relationship (QSAR) model that predicts mitochondrial accumulation of neuroleptics has been published, we investigated the effects of neuroleptics on white blood cell mitochondria. Venous blood samples were collected from both patients undergoing treatment with neuroleptics and healthy volunteers. The samples were processed for transmission electron microscopy. The resulting images of white blood cells were analyzed using stereology to compare quantitatively mitochondrial morphology in the patient and control groups. We found that in patients, but not in controls, there was swelling of mitochondria and fragmentation of the mitochondrial cristae. There also were fewer mitochondria in patients than in controls, although due to the swelling of the organelles, the volume density of mitochondria in the two groups was not significantly different. Such changes are typical of a toxic insult. Consequently, it seems plausible that, since schizophrenia is not a disease considered to affect white blood cells per se, these changes probably are due to the medication.     

Cardiolipin and its metabolites move from mitochondria to other cellular membranes during death receptor-mediated apoptosis

We previously reported that during death receptor-mediated apoptosis, cardiolipin (CL) relocates to the cell surface, where it reacts with autoantibodies from antiphospholipid syndrome sera. Here, we analysed the intracellular distribution of CL and its metabolites during the early phase of cell death signalling triggered by Fas stimulation in U937 cells and mouse liver. We found a redistribution of mitochondrial CL to the cell surface by using confocal microscopy and flow cytometry. Mass spectrometry revealed that CL and its metabolites relocated from mitochondria to other intracellular organelles during apoptosis, with a conversion into non-mitochondrial lipids. Concomitantly, cytosolic Bid relocated to the light membranes comprised in fraction P100, including the plasma membrane and associated vesicular systems. A direct Bid-CL interaction was demonstrated by the observation that CL and monolysoCL coimmunoprecipitated with Bid especially after Fas stimulation, suggesting a dynamic interaction of the protein with CL and its metabolites.     

Galactosylated N-vinylpyrrolidone-maleic acid copolymers: synthesis,characterization, and interaction with lectins

Water-soluble artificial glycoconjugate polymers were synthesized from poly(N-vinylpyrrolidone-co-maleic anhydride) by amidation with an amine-containing galactose derivative. The glycopolymers having different galactose contents were fully characterized in terms of chemical structure by NMR and potentiometric titrations, and their aqueous behavior was studied by viscometric measurements. Their specific binding properties were examined by enzyme-linked lectin assays using RCA(120) lectin. Whatever the glycopolymer, the grafted galactoses were shown to behave similarly to free galactose.     

Conversion of nucleotides sequences into genomic signals

An original tetrahedral representation of the Genetic Code (GC) that better describes its structure, degeneration and evolution trends is defined. The possibility to reduce the dimension of the representation by projecting the GC tetrahedron on an adequately oriented plane is also analyzed, leading to some equivalent complex representations of the GC. On these bases, optimal symbolic-to-digital mappings of the linear, nucleic acid strands into real or complex genomic signals are derived at nucleotide, codon and amino acid levels. By converting the sequences of nucleotides and polypeptides into digital genomic signals, this approach offers the possibility to use a large variety of signal processing methods for their handling and analysis. It is also shown that some essential features of the nucleotide sequences can be better extracted using this representation. Specifically, the paper reports for the first time the existence of a global helicoidal wrapping of the complex representations of the bases along DNA sequences, a large scale trend of genomic signals. New tools for genomic signal analysis, including the use of phase, aggregated phase, unwrapped phase, sequence path, stem representation of components'relative frequencies, as well as analysis of the transitions are introduced at the nucleotide, codon and amino acid levels, and in a multiresolution approach.     

Sodium cholate sorption on cationic dextran hydrogel microspheres. 1. Influence of the chemical structure of functional groups

New hydrogel microspheres based on crosslinked dextran, containing pendant quaternary ammonium groups with different chemical structures have been synthesized and tested as possible bile acid sorbents The in vitro sodium cholate sorption by these hydrogels has been followed in the absence or in the presence of competing anions The sorption results have indicated a strong influence of the chemical structure of functional groups on both the affinity and selectivity towards cholate ions. The best sorption performances were obtained with hydrogels having in the structure of functional groups an alkyl substituent with the length higher than C(8).