Dextran, clinical

Thoren L. The dextrans, clinical data. Dev Biol Stand 1981 48 157-167. 

Traditionally, Sephadex has been used for molecular weight analyses of proteins (Determan and Brewer, 1975) and clinical dextran (Granath and Kvist, 1967). Today, Sepharose, Sephacryl, or Superose is used for the assay of broad MWDs. Superdex is the premiere choice for attaining the highest resolution of components of similar size (see Fig. 2.1). 

The broad pore size distribution of Sepharose makes it well apt for the analysis of broad molecular mass distributions of large molecules. One example is given by the method for determination of MWD of clinical dextran suggested in the Nordic Pharmacopea (Nilsson and Nilsson, 1974). Because Superose 6 has the same type of pore size distributions as Sepharose 6, many analytical applications performed earlier on Sepharose have been transformed to Superose in order to decrease analysis time. However, Sepharose is suitable as a first try out when no information about the composition of the sample, in terms of size, is available. 

FIGURE 2.7 SEC elution profiles of dextran in clinical samples, serum ( ) and urine ( ). The first peak represent dextran and the second peak inulin (used as a reference for clearance). The content of carbohydrates was determined in collected fractions with the anthrone method. [Reproduced from Hagel ef of. (1993), with permission.]... 

There are also other immimological mechanisms, especially via IgG or IgM antibodies with immune complex formation, which can lead to similar clinical conditions [20, 34, 42] as has been shown in dextran anaphylaxis (table 1). Triggering of mast cells and basophils leads to release of various vasoactive mediators, among which histamine was the first recognized in 1908 (fig. 3,4) [6]. 

H, Devey ME Immunoglobulin class and subclass distribution of dextran-reactive antibodies in human reactors and non-reactors to clinical dex-tran. Allergy 1982 37 481-489. 

A summary of the properties of the different types of dextrans available is presented in Table 25.1. Dextrans for clinical use as plasma expanders must have moleeular weights between 40000 (= 220 glucose units) and 300000. Polymers below the minimum are excreted too rapidly fiom the kidneys, whilst those above the maximum are potentially dangerous because of retention in the body. In practice, infusions containing dextrans of average molecular weights of40000,70000 and 110000 are commonly encountered. 

Type of dextran Molecular weight (average) Product sterilization method Clinical uses... 

Iron-deficiency anemia in chronic PN patients may be due to underlying clinical conditions and the lack of iron supplementation in PN. Parenteral iron therapy becomes necessary in iron-deficient patients who cannot absorb or tolerate oral iron. Parenteral iron should be used with caution owing to infusion-related adverse effects. A test dose of 25 mg of iron dextran should be administered first, and the patient should be monitored for adverse effects for at least 60 minutes. Intravenous iron dextran then may be added to lipid-free PN at a daily dose of 100 mg until the total iron dose is given. Iron dextran is not compatible with intravenous lipid emulsions at therapeutic doses and can cause oiling out of the emulsion. Other parenteral iron formulations (e.g., iron sucrose and ferric gluconate) have not been evaluated for compounding in PN and should not be added to PN formulations. 

Claims have recently been made61 that the dextran of L. mesenteroides may serve as an efficient substitute for blood plasma. Solutions of partially-hydrolyzed dextran in saline gave favorable results when injected intravenously into experimental animals. Preliminary clinical tests were promising. 

Emphasis in the initial phase of our work was placed on sulfated polysaccharides that are antiviral. Not only were the desired rheological properties and long-term stability achieved in DCE formulations, the activity of the dextran sulfate or N9 were not compromised. DCE formulations containing DS display strong anti-HIV activity in vitro in comparison with negative (not shown) and positive controls (Figure 2). This is an important first step in the screening process towards clinical effectiveness. 

Bugelski, P. J., Ellens, H., Hart, T. K., and Kirsh, R. L. Soluble CD4 and dextran sulfate mediate release of gp 120 from HIV-l Implications for clinical trials. Journal of Acquired Immune Deficiency Syndromes 1991,4(9), 923-924. 

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. 

Dextrans of low molecular weight have also been fractionated by gel chromatography. Bremner and coworkers,67 in preparing (by alkaline degradation) dextrans of low molecular weight suitable for incorporation in the clinically important iron-dextran complex, fractionated their product on Sephadex G-50, with (O M sodium chloride as the eluant. Separate fractions, ranging in Mn (as determined by osmometry) from 1510 to 4860, were obtained in this way. 

The richest dietary sources of total iron are organ meats (liver and kidney), egg yolk, dried legumes, com, molasses and parsley. Liver is particularly valuable because of the high absorbability of its iron. However, only about 10% of dietary iron is absorbed. Iron deficiency anemia can be treated with soluble iron(II) compounds providing 200 mg in three or four daily divided doses. Oral iron(II) sulfate is the least expensive and is in wide use. Ascorbic acid increases the absorption efficiency of iron(II) sulfate. Parenteral administration of iron is used when oral iron is ineffective. Iron-dextran, a colloid formed from iron(III) chloride and an alkali-modified dextran, is one of several preparations available which has found extensive clinical use. It contains up to 28% Fe by weight and has a structural similarity to ferritin. Transfusion therapy may also be used in severe chronic anemia or acute hemorrhage. 

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