Dextran, clinical agents

On the positive side, dextran itself has been refined and employed as a therapeutic agent in restoring blood volume for mass casualties. Natural dextrans have very high molecular weight (on the order of 10 -10 Da) and are found to be unsuitable as a blood-plasma substitute. Lower molecular weight (about 10 Da) dextran is suitable and often referred to as clinical dextran. 

Hematological agents In clinical trials in patients undergoing PTCA/PCI, coadministration of bivalirudin with heparin, warfarin, thrombolytics, or GPIIb/llla inhibitors was associated with increased risks of major bleeding events compared with patients not receiving these concomitant medications. There is no experience with coadministration of bivalirudin and plasma expanders such as dextran. 

Velocity gradients in blood vessels are reduced in cases of retarded peripheral circulation, especially in shock. Under these conditions erythrocytes may aggregate and the discovery of agents that are capable of reducing this stmctural viscosity is thus of great clinical value. Dextrans and polyvinylpyrrolidones diminish attraction between individual cells in blood and improve flow properties. 

Clinically important, potentially hazardous interactions with amiodarone, clarithromycin, clopidogrel, desirudin, dextran, fondaparinux, gpiib/iiia receptor antagonists, heparin, quinidine, rifampin, St John s wort, sulfinpyrazone, thrombolytic agents, tidopidine, verapamil, vitamin k antagonists... 

After Ed s move to Einstein in 1956, a joint U.S. patent in the public interests was filed (together with H. M. Tsuchiya and N. N. Heilman) on the practical production of the Streptococcus DS-50 dextran. Pilot plant production was undertaken at NRRL clean-up and bottling were carried out as a service by the Cutter Corp. and a successful clinical trial of the dextran for treatment of patients in shock was conducted by Dr. W. Metcalf of Einstein s Department of Surgery. Ed presented a final report to the National Research Council in 1962. In the end, despite the discovery of a simpler way to manufacture a product of great potential military usefulness, dextran in general would be replaced by blood and plasma as agents of plasma volume expansion in shock patients. 

The iron oxide nanoparticles are coated in polysaccharides (dextran or carboxydextran) to make them hiocompatihle and are administered to patients as aqueous colloids. Clinical MRI contrast agents of this type include Feridex, Resovist and Combidex which are selectively taken up hy the liver, spleen and bone marrow. The S5mthesis and potential applications in MRI of related iron oxide nanoparticles is currently an active area of research. 

The antiviral properties of anionic polymers have recently received a lot of attention as agents to protect against infection with sexually transmitted diseases. Due to the cationic nature of most viruses, several anionic polymers are known to bind viruses. As early as the 1960s, researchers had studied the anti-viral properties of a variety of synthetic polymers [118]. However, not all anionic polymers inactivate viruses. Several classes of anionic polymers have been studied for their ability to inactivate the HIV virus. These polymers include poly(styrene-4-sulfonate), 2-naphthalenesulfonate-formaldehyde polymer, and acrylic acid-based polymers. Certain chemically modified natural polymers (i.e., semisynthetic) such as dextrin/dextran sulfates, cellulose sulfate, carrageenan sulfate, and cellulose acetate phthalate have also been investigated for this purpose. Of a number of such anionic polymers that have shown in-vitro and in vivo anti-HIV activity, a couple of polymeric drug candidates have proceeded to early stage human clinical trials for the evaluation of safety/tolerability [119]. While most of these have shown the desired tolerability and safety, further clinical trials are necessary to discern the therapeutic benefit and see if anionic polymers will be applicable as anti-HIV therapies. 

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