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Biomedical subjects

D Sabolovic

Publications and source records attributed to D Sabolovic.

At least 19 recordsLinked to original sources
PubMed2001

Magnetic resonance of a dextran-coated magnetic fluid intravenously administered in mice.

Magnetic resonance was used to investigate the kinetic disposition of magnetite nanoparticles (9.4 nm core diameter) from the blood circulation after intravenous injection of magnetite-based dextran-coated magnetic fluid in female Swiss mice. In the first 60 min the time-decay of the nanoparticle concentration in the blood circulation follows the one-exponential (one-compartment) model with a half-life of (6.9 +/- 0.7) min. The X-band spectra show a broad single line at g approximately 2, typical of nanomagnetic particles suspended in a nonmagnetic matrix. The resonance field shifts toward higher values as the particle concentration reduces, following two distinct regimes. At the higher concentration regime (above 10(14) cm(-3)) the particle-particle interaction responds for the nonlinear behavior, while at the lower concentration regime (below 10(14) cm(-3)) the particle-particle interaction is ruled out and the system recovers the linearity due to the demagnetizing field effect alone.

Animals↗
PubMed2000

Covalent binding of polyethylene glycol to the surface of red blood cells as detected and followed up by cell electrophoresis and rheological methods.

Cyanuric chloride activated polyethylene glycol (PEG)-5000 was covalently coupled to murine and human red blood cells (pegylated RBC). Our purpose was to camouflage RBC receptors, which is necessary for parasite invasion, a process essential to sustain parasitemia. Cell electrophoretic mobility analysis (CEM) of pegylated RBC distinguished a new population of cells bearing characteristic CEM. Pegylation of RBC also modified their rheological properties, which were documented by evaluation of cell deformability (based on cell transit time through calibrated micropores) and cell aggregation (as measured by ultrasonic interferometry). Homologous transfusion of pegylated RBC into murine malaria-infected mice had no significant effect on the cerebral malaria death rate in Plasmodium berghei-infected mice, but it reduced the peripheral blood parasitemia by a factor 2 while in Plasmodium yoelii infected mice, the parasitemia was dramatically reduced by a factor of 4. These experiments demonstrate that transfusion of pegylated RBC may inhibit peripheral parasitemia. Cell electrophoresis appears to be a useful tool to allow in vivo detection and to investigate the fate of transfused pegylated RBC.

Animals↗
PubMed2000

Blood compatibility of particulate carriers investigated by cell electrophoresis and particle electrophoresis: a preliminary report.

Polyethylene glycol (PEG) and dextran were covalently coupled, or only adsorbed, to the surface of three kinds of inorganic particles in order to shield their surface and reduce their nonspecific binding to red blood cells. Surface modification as well as interaction of particles with red blood cells was followed up by particle electrophoresis. This allowed a quick evaluation of the efficiency of polymer coupling. Moreover, the nonspecific binding of particles to red blood cells was easily investigated with cell electrophoresis, showing the inhibitory effect of immobilized PEG-5000 or dextran. The electrophoretic mobility analysis presented here may be used for screening blood compatibility of particulate drug carriers and could be helpful in formulating long-living circulating particles.

Animals↗
PubMed1998

Characterization of a subpopulation of mouse red blood cells as preferential target for malarial invasion.

Cell electrophoresis was used to study a distinct subpopulation of murine red blood cells (RBC). These RBC are normally found in the spleen and bone marrow. They appear in the peripheral blood when mice are mildly bled or sucked by mosquitos. These cells have been characterized as having larger size, light density, lower electrophoretic mobility, and being more resistant to lysis with unsaturated fatty acids and in glycerol-containing medium than mature erythrocytes. All their features suggest that their differentiation status represents an intermediate stage between reticulocytes and adult RBC. In vitro Plasmodium invasion tests showed their increased sensitivity to invasion by the parasites. The extent of their spreading in the blood was found to be strain-dependent, being more pronounced in C57B1/6 mice, highly susceptible to developing cerebral malaria after infection with Plasmodium berghei, as compared to Balb/c, a nonsusceptible strain of mice.

Animals↗
PubMed1998

Surface modification of superparamagnetic nanoparticles (Ferrofluid) studied with particle electrophoresis: application to the specific targeting of cells.

Colloidal aqueous suspension of superparamagnetic nanoparticles (9 nm in diameter) composed of maghemite (gamma Fe2O3) and forming an ionic ferrofluid in aqueous solution are covalently coupled with lectins, enzymes or antibodies, using specific thiol chemistry. The surface charge modifications of nanoparticles, caused by ligand coupling, were monitored by measuring their electrophoretic mobilities using laser-Doppler velocimetry. Particle electrophoretic mobility (PEM) changes are shown to correlate well with the amount of ligand fixed on the particles, as probed by its biological activity. The PEM method provides a useful tool to optimize ligand immobilization at the surface of nanoparticles, and may be advantageous when biological activity measurements are not convenient.

Animals↗
PubMed1998

Cell electrophoretic mobility and glycerol lysis of human erythrocytes in various diseases.

Using an automated cell electrophoresis system equipped with an image processor, we studied electrophoretic mobilities of erythrocytes of healthy donors and of patients suffering from systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), hypergammaglobulinemia and diabetes mellitus (DM). On average, erythrocytes from SLE patients showed mean electrophoretic mobilities (EPM) which were significantly lower (p < 0.005) than the EPM of red blood cells of normal donors. Evaluation of mean EPM and standard deviations revealed that three groups of SLE patients could be distinguished regarding the electrophoretic behavior of their erythrocytes. Some patients had red blood cells with normal EPM, others had erythrocytes with significantly reduced EPM, and a third group appeared to have both kinds of erythrocytes. In addition, erythrocytes of various SLE patients showed enhanced resistance to lysis by glycerol and their membranes contained less quantities of band 3 proteins.

Arthritis, Rheumatoid↗
PubMed1998

Particle electrophoresis of micrometric-sized superparamagnetic particles designed for magnetic purification of cells.

Measuring the electrophoretic mobility of superparamagnetic particles (0.5-4.5 microns mean size) was undertaken to probe the coupling of lectins and antibodies to their surface. Coupling was either noncovalent (antigen-antibody and biotin-streptavidin linkage) or covalent (tosyl-activated beads). The direct observation of the electrophoresis of single particles illuminated in dark field and processed by image analysis allowed the determination of their apparent electrophoretic mobility. Mobilities ranged from -0.5 micron s-1/CmV-1 to +1 micron s-1/CmV-1 when measured at 20 degrees C in 0.15 M NaCl and 30 mg/mL sorbitol, pH 7.4. The relative standard deviation was less than 0.1%. Surface immobilization of charged proteins onto the superparamagnetic beads shifted their electrophoretic mobility up to 200%; this was also quantitatively correlated with some specific properties (enzymatic activity, antigen-binding activity, lectin-binding activity). Although particle electrophoresis has mainly been reported for the study of surface adsorption phenomenon, it may be a versatile tool for controlling covalent modifications of particles designed for therapeutical targeting or chromatographic use and may also apply to a quantitative analysis of ligand-binding interactions.

Biotin↗
PubMed1997

Membrane modifications of red blood cells in Alzheimer's disease.

Red blood cells (RBC) from 24 Alzheimer's disease (AD) patients, 18 age- and sex-matched nondemented (ND) patients, hospitalized in the same facility for orthopedic problems, and 18 healthy volunteers aged 30-52 years were studied in order to gain insight into the nature of RBC membrane modifications in AD. Significant differences were found between RBC from AD and ND patients or young controls respectively for annexin V-binding (45.5 +/- 18.0% vs 27.1 +/- 14.7 and 2.7 +/- 1.9, p = .003), fraction of glycerol resistant cells (30.8 +/- 11.1% vs 19.6 +/- 6.4 and 10.2 +/- 3.1, p = .026), cell electrophoretic mobility in polymer (1.028 +/- 0.022 microns sec-1 V-1 cm vs 1.046 +/- 0.022 and 1.053 +/- 0.021, p = .02) and only limited significance for the filterability (1.46 +/- 0.12 msec vs 1.58 +/- 0.11 and 1.54 +/- 0.11, p = 0.1). A logistic analysis, using simultaneously several features as independent variables, suggested the combined use of annexinV- binding, glycerol resistance, and cell filterability which allowed the assignment of 95% of patients from this cohort to the right group. A prospective analysis of a larger cohort is required for the estimation of the diagnostic value of this test battery. In addition, the high level of annexin binding is characteristic of a disruption of the phospholipid asymmetry in aged or damaged cells, while the high glycerol resistance combined with low electrophoretic mobility an rigidity characterize young RBC, thus indicating an enhanced turnover of RBC in Alzheimer's disease.

Adult↗
PubMed1995

Effect of fatty acid treatment in cerebral malaria-susceptible and nonsusceptible strains of mice.

Cerebral malaria-susceptible (C57BL/6) mice infected with Plasmodium berghei ANKA (PbA) developed low parasitemia and died from typical neurological symptoms between 8 to 10 days after infection. In contrast, nonsusceptible (BALB/c) mice developed high peripheral blood parasitemia and died 22-24 days later without neurological implications. Daily injections of fatty acids (FA) during the first 3 days after infection protected C57BL/6 mice from cerebral symptoms but had no effect on BALB/c mice. Thus, treated C57BL/6 mice developed hyperparasitemia and died 25 days after infection, like BALB/c mice. Red blood cells from C57BL/6 control mice were found to be more resistant to lysis by linoleic acid than those of BALB/c mice. Three days following infection with PbA, these differences disappeared. Treatment with FA prevented these changes. We concluded that the host's cells were altered soon after infection and that the nature and degree of alterations depended on the mouse strain, thus determining the eventual outcome of the infection. Likewise, the effects of FA might not be directed against the parasite but rather seem to act early after infection on these parasite-induced modifications of host cells.

Animals↗
PubMed1995

Use of annexin V-ferrofluid to enumerate erythrocytes damaged in various pathologies or during storage in vitro.

Recombinant human annexin V was bound covalently to 9 nm maghemite (gamma Fe2O3) nanoparticles, yielding annexin-ferrofluid (AnxFF), and used to separate annexin-bound red blood cells (RBC) in a magnetic field and estimate their percentage in various bloods. Annexin binding in normal human RBC increased proportionately with storage from 8% on day 2 to 42% on day 100. Enhanced AnxFF binding was associated with various pathologies. Thus, normal blood contained 10.7 +/- 5.9% AnxFF binding RBC; bloods with normal sedimentation rates (albeit with some disease necessitating analysis) contained 23.5 +/- 6.2%; those with high sedimentation rates contained 51.5 +/- 12.3%; sickle cell anaemia patients' blood contained 50.0 +/- 9.3%, and bloods from patients with other pathologies (deforming rheumatic disease, cancer necessitating chemotherapy, etc.) contained 58.6 +/- 7.6% AnxFF binding RBC. Enhanced Ca+2-dependent annexin binding reflects a loss of the asymmetric distribution of anionic phospholipids in plasma membranes which may constitute a signal for the destruction of the modified cells by the reticuloendothelial system. Once these preliminary results are confirmed, the determination of the fraction of AnxFF bound erythrocytes, following their magnetic separation, could prove a simple and rapid quality test for example in the context of blood transfusion.

Anemia, Sickle Cell↗
PubMed1994

Alterations of uninfected red blood cells in malaria.

Red blood cell (RBC) negative charges and resistance to linoleic acid (LNA)-induced lysis were studied in Plasmodium yoelii-infected mice and in malaria (P. falciparum)-affected individuals. RBCs from mice infected with P. yoelii showed a progressive decrease in the net surface negative charges at 24 h after infection, reaching a minimal value on day 3, followed by a second phase that was characterised by a recovery to normal levels on day 6. Resistance to linoleic acid follows similar kinetics. These alterations preceded the appearance of parasites in the peripheral blood. A similar increase in LNA-induced lysis was observed in RBCs from malaria-affected individuals. These early membrane alterations of uninfected RBCs could be responsible for spreading of infection and RBC lysis during infection.

Adult↗
PubMed1992

Cyclophosphamide-induced suppressor cells in nude mice.

Lymphocytes regenerated after treatment with a high dose of cyclophosphamide (CY) were characterized in nude mice. Ten days after a single injection of 200 mg/kg CY into nude mice, regenerated spleen cells suppressed in vitro primary and second antibody production against sheep red blood cells. The CY-treated spleen cells exhibited normal natural killer (NK) activity, very low B and T cell content, but increases in cell surface charge [electrophoretic mobility (EPM)] and histamine receptors. The suppressor cells could not be removed by treatment with anti-Thy-1 plus complement (C), or treatment with antiasialo GM1 (aGM1) plus C, which abrogated NK activity. It was concluded that CY-treated spleen cells, which exhibited high EPM and histamine receptors, comprise the natural suppressor cells which are Ig-, Thy-1- and aGM-1.

Animals↗
PubMed1988

Clinical improvement in advanced cancer disease after treatment combining histamine and H2-antihistaminics (ranitidine or cimetidine).

In a randomized study 31 patients with advanced cancer disease in whom classical anticancer therapy had been abandoned received a daily combination of subcutaneous histamine and oral H2-antihistaminics. In 27 patients, treatment induced a marked clinical improvement as shown by a large rise in performance status (Karnofsky scale). Ten patients were still alive 3-14 months after initiation of treatment. Average survival in the 31 treated patients (172 +/- 113 days) was significantly longer than in 34 non-treated patients with similar advanced cancer (26 +/- 16 days, P less than 0.00001). In six treated patients, the size of liver and lung metastases decreased. Histamine was perfectly tolerated up to 4 mg/day.

Adult↗
PubMed1986

Effect of a protein bound polysaccharide (PS-K) on tumor development and infections in splenectomized rats and mice.

Daily oral administration of PS-K, an immunomodulating agent, was found to improve survival rate in tumor bearing mice and rats and to decrease susceptibility to infection in mice. Surprisingly, splenectomized tumor bearing rats and mice responded better to PS-K treatment as measured by survival rate, tumor size and immunosuppressive properties of serum. The mechanism of PS-K antitumor activity in both experimental systems might be due to the alteration of splenic immune suppressive mechanisms during tumor growth in the host. On the other hand, host resistance to acute infection was found to be less dependent upon the presence or absence of spleen suggesting a different mechanism of PS-K activity in acute infectious disease.

Administration, Oral↗
PubMed1981

Spontaneous maze ambulation in two mouse strains.

A simple device is described, which permits us to quantify several parameters of spontaneous behaviour of small animals. Using this device with mice we obtained statistically satisfactory results, showing a strong genetic influence on the behavioural characteristics tested.

Animals↗