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Biomedical subjects

S Margel

Publications and source records attributed to S Margel.

At least 37 records · Page 2Linked to original sources

Iron detoxification by haemoperfusion through deferoxamine-conjugated agarose-polyacrolein microsphere beads.

The natural iron chelator deferoxamine was bonded to agarose-polyacrolein microsphere beads (APAMB). This novel deferoxamine-conjugated APAMB (DCA), when used as the sorbent in a plasma/haemoperfusion system, showed specific and rapid removal of iron from plasma and blood in vitro; in vivo experiments also showed specific iron removal. The advantages of this sorbent are minimal damage to biocompounds during haemoperfusion, high capacity and specificity to iron, and the possibility of reuse.

Acrolein↗

Development of a novel C1q immunoadsorbent for removal of circulating immunecomplexes: quantitative isolation of hepatitis B virus surface antigen and immunecomplexes.

A technique for large scale production of human C1q from plasma by affinity chromatography on an anti-C1q column is described. Affinity purified C1q was covalently coupled to a newly developed agarose polyacrolein microsphere beads immunoadsorbent. This immunoadsorbent was utilized for quantitative removal of artificially formed bovine serum albumin (BSA)-anti-BSA immune complexes (IC). The C1q affinity column was then used for the isolation of immunecomplexes containing hepatitis B virus (HBV) surface antigen (HBsAg) from serum of an HBsAg carrier. Identical columns may be utilized for quantitative removal of a variety of IC from blood of patients with infectious and autoimmune diseases, as well as neoplastic diseases. Furthermore, dissociated immunecomplexes will provide an additional source for purification of specific antigens.

Animals↗

Agarose-polyacrolein microsphere beads: a new microcarrier culturing system.

A new microcarrier (MC) culturing system for anchorage-dependent cells is described. The system is based on polyacrylein microspheres encapsulated in agarose and derivatized by various amino ligands. In practice, any protein or ligand with primary amino groups may be covalently bound to the microspheres through their aldehyde groups. The ease with which the beads may be derivatized enables the preparation of MC with desired surface properties for growing a variety of cells. In this model system the beads were derivatized by 2-(diethylamino)ethylamine (DEAE), diaminohexane (DAH), poly-L-lysine (PL), gelatin and collagen. The derivatized beads supported the growth of primary cells, diploid cell strains and established cell lines for biological studies as well as for production of various cell products.

Acrolein↗

The rabbit as an animal model for haemoperfusion: surgical preparation and use.

In this paper the authors describe the surgical procedure to prepare rabbits for haemoperfusion experiments. The carotid artery and jugular vein are cannulated and a simple shunt device inserted to maintain patency of the vessels over a period of time. The cannulas and shunt remain patent and free of infection for some months. Specially designed outflow and inflow extracorporeal tubing sets minimize blood volume outside the body of the rabbit. The authors also illustrate the efficacy of this system in haemoperfusion trials to remove specific antibodies. Recently a system was described to remove mercury from the bloodstream of poisoned animals. The rabbit is a useful experimental animal for this type of haemoperfusion trial.

Animals↗

Specific removal of digoxin by hemoperfusion through agarose polyacrolein microsphere polyacrolein microsphere beads-antidigoxin antibodies (APAMB-AD).

The efficacy of a new, biocompatible, specific immunosorbent for hemoperfusive removal of digoxin is described. The sorbent contains antidigoxin antibodies covalently bound to polyacrolein microspheres, 0.2 mu diam. Thousands of microspheres are matrix-encapsulated in crosslinked agarose to form beads of 500 to 800 mu diam. Digoxin intoxicated dogs showed heart block, ventricular and atrial tachycardia and extended runs of PVCs. During hemoperfusion the abnormal ECG abated; at 2 h of hemoperfusion the ECG tracings returned to normal. Up to 25% of the total digoxin burden was removed. The numbers of the blood cells and the content of a battery of relevant soluble components of the blood remained constant. Dogs were alive and well after the hemoperfusion. Non hemoperfused dogs, which received antiarrythmic agents, did not survive the intoxication. This is the first report of a practical hemoperfusive system for the specific removal of digoxin from whole blood.

Acrolein↗

Reduction of organic mercury in water, urine, and blood by sodium borohydride for direct determination of total mercury content.

We have established the optimal conditions for use of sodium borohydride as the reducing agent before the direct determination of mercury in water, urine, and blood by atomic absorption spectroscopy. We evaluated the effects of pH, temperature, and cupric sulfate concentration on the direct determination of both organic and inorganic compounds of mercury. Accurate and precise quantification of mercury requires that the pH be between 9.3 and 9.5, the reaction temperature above 25 degrees C, the reaction time longer than 1 min, and, for urine samples only, the cupric sulfate concentration 10 mumol/L. The detection limit of the method is 1 to 2 ng and the precision (CV) is 3.8% for blood and 4.0% for urine.

Borohydrides↗

Novel effective immunoadsorbents based on agarose-polyaldehyde microsphere beads: synthesis and affinity chromatography.

Agarose-polyaldehyde microsphere beads were produced by encapsulating polyacrolein microspheres or polyglutaraldehyde microspheres with agarose. Magnetic beads were formed by carrying out the encapsulation procedure in the presence of ferrofluidic particles. Proteins were bound covalently, at physiological pH, to the beads through their aldehyde groups to produce the Schiff base products. The conjugates, beads-proteins, were used successfully in affinity chromatography for specific purification of antibodies. Leaching of the proteins bound to the beads under physiological conditions and eluting conditions was not detected. The agarose-polyaldehyde microsphere beads are suggested as alternatives to the supports currently used in affinity chromatography.

Animals↗

Hemoperfusion with chelating microspheres as a new treatment for severe mercury poisoning.

Monodisperse beads of 1.0 mm diameter composed of polymercaptal microspheres of 0.8 micron average diameter encapsulated with agarose were prepared. The polymercaptal microspheres have high affinity for organic and inorganic mercury compounds and do not bind to alkali and alkaline earth metalic compounds. The agarose-polymercaptal microsphere beads (APMMB) are blood compatible with high porosity. In vitro experiments with a column containing these beads illustrated their efficiency for the removal of mercury from the blood by means of hemoperfusion.

Biocompatible Materials↗

Agarose-polyaldehyde microsphere beads: synthesis and biomedical applications. Cell labeling, cell separation, affinity chromatography, and hemoperfusion.

Polyaldehyde microspheres, polyglutaraldehyde (PGL), and polyacrolein (PA) were synthesized by polymerizing glutaraldehyde and acrolein in the presence of an appropriate surfactant. The microspheres with average diameter of 0.2 micron were used for the specific labeling of human red blood cells (RBC) and mouse lymphocytes. The "naked" microspheres were encapsulated with agarose and formed agarose-polyaldehyde microsphere beads in sizes ranging from 50 microns up to 1 cm. The encapsulated beads, with diameters ranging from 50 to 150 microns were used as insoluble adsorbents for affinity purification of antibodies. Beads with diameters varied from 150 to 250 microns were used for cell fractionation purposes (mouse B splenocytes from T splenocytes). Uniform beads of 1 mm diameter were designed for hemoperfusion purposes. As a model, the removal in vitro of anti-BSA from immunized goat whole blood was studied.

Acrolein↗

Cell fractionation with affinity ligands conjugated to agarose-polyacrolein microsphere beads.

A new effective insoluble support useful for cell fractionation based on agarose-polyacrolein microsphere beads (APAMB) of diameters 150--250 micrometers has been developed. The synthesized polyacrolein (PA) microspheres, of average diameter 0.2 micrometer, are provided with reactive aldehyde groups through which various ligands containing primary amino groups are bound covalently in a single step at physiological pH. Antibodies coupled to the microspheres are very effective for labelling of cell surface receptors on human red blood cells and mouse lymphoid cells. APAMB were obtained by encapsulating the PA microspheres with agarose. Antibodies and lectins bound to the APAMB serve to construct affinity columns for the separation of red blood cells and murine lymphocyte subpopulations. Anti-human red blood cell antibodies coupled to anti-immunoglobulin APAMB are effective in separating human from turkey red blood cells, whereas either anti-Thy 1.2 anti-immunoglobulin antibodies or soybean agglutinin coupled to APAMB have proved useful for the separation of T and B cells from heterogeneous population of spleen cells. The separation procedure is simple, rapid and effective. The viability of the fractionated cells is unaffected by the procedure and the recovery of the cells is high: between 80% and 100%.

Acrolein↗

Chelation of mercury by polymercaptal microspheres: new potential antidote for mercury poisoning.

Newly synthesized polymercaptal microspheres of 0.8 +/- 0.02 micron were shown to have a specific and fast intake of mercury compounds over a whole range of pH while maintaining low toxicity. The microspheres bind easily with mercury compounds which are already bound to the biological mercury binders, albumin or cysteine. Mercury was recovered completely from the microspheres by using a solution of thiourea in hydrochloric acid. Due to their high surface area, low toxicity, and strong affinity toward mercury compounds, the microspheres have a potential use as a new oral drug for treatment in cases of mercury poisoning.

Antidotes↗

Polyacrolein microspheres as a new tool in cell biology.

Polyacrolein (PA) microspheres in sizes ranging from 0.04 micron to 40 microns were synthesized. Magnetic and fluorescent PA microspheres were formed by carrying out the polymerization process in the presence of appropriate ferrofluidic or fluorochromic compounds, respectively. The microspheres carry reactive aldehyde groups, through which various ligands, containing primary amino groups, were covalently bound at physiological pH values. The potential use of these microspheres was demonstrated by the specific labelling of fresh human red blood cells (RBC) and by the separation of human RBC from turkey RBC by means of a magnetic field. PA microspheres were also bound covalently to the anti-allergic drug disodium chromoglycate (DSCG) and the conjugate was used for the labelling of rat basophilic leukaemia cells.

Acrolein↗

A new immunoadsorbent for hemoperfusion: agarose-polyacrolein microspheres beads. I. In vitro studies.

The development and properties of a novel adsorbent system consisting of polyacrolein microspheres encapsulated in agarose is described. In the model system, the microspheres contain covalently bound bovine serum albumin. In practice any protein or ligands with primary amino groups may be covalently bound. Circulating antibovine serum albumin antibodies were adsorbed from whole blood or serum of rabbits or goats onto the microspheres. The capacity of this batch is 10 mg antibody adsorbed/gm wet weight beads. When the column is operated at less than capacity, 50%, 70%, 90% and 95% of the anti BSA is adsorbed in 30, 60, 120 and 180 min, respectively. Thus, relatively short periods of hemoperfusion may be used. The beads are biocompatible. There are negligible decreases of RBC; up to a 10% decrease of WBC and up to a 20% decrease of platelets in 3 hrs. The beads are stable; neither breakdown nor leakage was observed over a period of 3 months. High flow rates were readily obtained. The mean diameter of the microspheres is 0.2 mu; the mean diameter of the agarose polyacrolein microspheres beads (APAMB) is 1.0 mm. We can produce monodisperse beads of any given diameter ranging from 200 mu to 1 cm.

Acrolein↗

A novel approach for heavy metal poisoning treatment, a model. Mercury poisoning by means of chelating microspheres: hemoperfusion and oral administration.

The chelating drugs BAL (2,3-dimercaptopropanol), EDTA (ethylenediaminetetraacetic acid), and penicillamine (2-amino-3-mercapto-3-methylbutanoic acid), which are used for metal poisoning, are toxic and there is a real need for alternatives, especially for severe cases. A novel approach for treatment of heavy-metal poisoning is under investigation in our group. The approach utilizes the synthesis of chelating microspheres specific for the desired metallic compound. The microspheres are suggested for use in severe cases by means of hemoperfusion, as a first aid, and then by oral administration. As a model this approach was tried for mercury poisoning. Polymercaptal microspheres of 0.8 micrometer average size were synthesized. The microspheres have a high surface area, have a high affinity toward organic and inorganic mercury compounds, and can compete easily with albumin and cysteine in the ability to bind mercury compounds. These microspheres also were encapsulated with agarose--a blood compatible polymer--and were tried successfully for plasma perfusion (in 10 min, 40% of CH3HgCl and of HgCl2 were removed from 20 ppm of poisoned plasma).

Administration, Oral↗

A novel synthesis of polyacrolein microspheres and their application for cell labeling and cell separation.

A novel method for the synthesis of polyacrolein microspheres with fluorescent or magnetic properties is described. These microspheres carry reactive aldehyde groups on their surface, which are used for covalent binding of various proteins at physiological pH. Polyacrolein microspheres may be used as a simple tool for cell labeling and cell separation. The feasibility of specific labeling of fresh human red blood cells and of the separation of human red blood cells from turkey red blood cells by means of a magnetic field is discussed.

Acrolein↗

Hemoperfusion for detoxification of mercury. A model:treatment of severe mercury poisoning by encapsulated chelating spheres, Part I.

Polymercaptal microspheres of average size 0.8 mu were synthesized. They have very high affinity towards mercury compounds and do not interact with alkali or alkali earth metallic compounds, they can also easily bind mercury compounds which were already bound to albumin or cysteine. Polymercaptal spheres were encapsulated by agarose--a blood compatible polymer. The encapsulated spheres were used successfully by means of plasma perfusion for detoxification of organic and inorganic mercury compounds from poisoned plasma.

Capsules↗

Electrophoretic cell separation by means of microspheres.

The electrophoretic mobility of fixed human erythrocytes immunologically labeled with poly(vinylpyridine) or poly(glutaraldehyde) microspheres was reduced by approximately 40%. This observation was utilized in preparative scale electrophoretic separations of fixed human and turkey erythrocytes, the mobilities of which under normal physiological conditions do not differ sufficiently to allow their separation by continuous flow electrophoresis. We suggest that resolution in the electrophoretic separation of cell subpopulations, currently limited by finite and often overlapping mobility distributions, may be significantly enhanced by immunospecific labeling of target populations using microspheres.

Animals↗