Morphological Findings Following Single or Multiple Administration of Gelatin Plasma Substitutes

Kief, H

doi:10.1159/000384859

Cited by 3 publications

(1 citation statement)

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“…Daily dose used in that study was much higher than a dose of Dex40-GTMAC3 used in our study to neutralize high dose of UFH (prolonging activated partial thromboplastin time more than 15 times). Osmotic nephrosis-like lesions were reported for other biopolymers such as hydroxyethyl starches (Legendre et al, 1993 ) and gelatins (Kief, 1969 ). They were also observed with agents that do not induce acute renal failure such as mannitol and glucose (Kief, 1969 ).…”

Section: Discussionmentioning

confidence: 93%

The Toxicokinetic Profile of Dex40-GTMAC3—a Novel Polysaccharide Candidate for Reversal of Unfractionated Heparin

et al. 2016

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Though protamine sulfate is the only approved antidote of unfractionated heparin (UFH), yet may produce life threatening side effects such as systemic hypotension, catastrophic pulmonary vasoconstriction or allergic reactions. We have described 40 kDa dextrans (Dex40) substituted with glycidyltrimethylammonium chloride (GTMAC) as effective, immunogenically and hemodynamically neutral inhibitors of UFH. The aim of the present study was to evaluate in mice and rats toxicokinetic profile of the most promising polymer—Dex40-GTMAC3. Polymer was rapidly eliminated with a half-time of 12.5 ± 3.0 min in Wistar rats, and was mainly distributed to the kidneys and liver in mice. The safety studies included the measurement of blood count and blood biochemistry, erythrocyte osmotic fragility and the evaluation of the histological alterations in kidneys, liver and lungs of mice and rats in acute and chronic experiments. We found that Dex40-GTMAC3 is not only effective but also very well tolerated. Additionally, we found that protamine may cause overt hemolysis with appearance of permanent changes in the liver and kidneys. In summary, fast renal clearance behavior and generally low tissue accumulation of Dex40-GTMAC3 is likely to contribute to its superior to protamine biocompatibility. Intravenous administration of therapeutic doses to living animals does not result in the immunogenic, hemodynamic, blood, and organ toxicity. Dex40-GTMAC3 seems to be a promising effective and safe candidate for further clinical development as new UFH reversal agent.

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Section: Discussionmentioning

confidence: 93%

The Toxicokinetic Profile of Dex40-GTMAC3—a Novel Polysaccharide Candidate for Reversal of Unfractionated Heparin

et al. 2016

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The effects of arginine, dextran and Haemaccel infusions on urinary albumin, β2-microglobulin and

O’Reilly

Parry²,

Whicher

1986

Clinica Chimica Acta

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Tissue deposits of hydroxyethyl starch (HES): dose-dependent and time-related

Sirtl

Laubenthal

Zumtobel

et al. 1999

British Journal of Anaesthesia

132

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Tissue deposits occur after administration of plasma substitutes. After hydroxyethyl starch (HES), deposits may last for months, causing pruritus and impairment of function. Because elimination of HES deposits has not been demonstrated in humans, we studied 26 patients, for up to 7 yr after HES administration, to assess HES storage. HES dose ranged from 0.34 to 15.00 g kg-1 body weight, and administration intervals from 1 day to 7 yr. Biopsies of the liver, muscle, spleen, intestine or skin were studied using light and electron microscopy and immunohistochemistry. HES storage was dose-dependent, decreased in all organs with time and was greater in patients suffering from pruritus. We conclude that tissue deposition of HES is transitory and dose-dependent, with differences between subjects in severity and duration.

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Morphological Findings Following Single or Multiple Administration of Gelatin Plasma Substitutes

Cited by 3 publications

References 0 publications

The Toxicokinetic Profile of Dex40-GTMAC3—a Novel Polysaccharide Candidate for Reversal of Unfractionated Heparin

The Toxicokinetic Profile of Dex40-GTMAC3—a Novel Polysaccharide Candidate for Reversal of Unfractionated Heparin

The effects of arginine, dextran and Haemaccel infusions on urinary albumin, β2-microglobulin and

Tissue deposits of hydroxyethyl starch (HES): dose-dependent and time-related

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