Tackling the acute radiation syndrome: Hemoperfusion with activated carbon revisited.

Almost three decades ago Dr. Nikolaev and co-authors reported a remarkable finding that a single-course low-volume hemoperfusion through uncoated spherical activated carbon led to a significant increase in survival of dogs acutely irradiated with X-rays of the dose of 5.25 Gy (Artif. Organs. 1993; 17: 362-8). In those studies, the adsorptive detoxification, which is characteristic for carbon adsorbents, was less likely to play a predominant role in radioprotection, thus prompting the authors to assume that some other, unknown, mechanisms were involved. This article is aimed to interpret the radioprotective effect of activated carbon, based on the mounting evidence that it is capable of reducing the oxidative stress and promoting the recovery in various tissues and organs (including hematopoietic) with an active involvement of relatively radioresistant tissue-resident macrophages.

Densitometry of the optically magnified dried residues representing carbon microparticles as a simple and affordable technique for determining their concentrations in aqueous suspensions.

In extracorporeal blood purification, such as hemoperfusion, activated carbon (activated charcoal) beads are commonly used as an adsorbent, but their judgment in terms of extent of microparticle release is of great importance since the microparticles may represent the risk of entering the bloodstream. To quantitatively assess the release of carbon microparticles (CMPs) in the samples of the aqueous perfusion medium, in which the beads have been perfused, the calibration procedure with different concentrations of CMPs is likely to be needed. For this purpose, carbon beads were mechanically crushed to a fine powder, whose microparticles (<10 µm) were then serially diluted in the aqueous medium within the wide range of concentrations (0.2-100 µg/ml). To test these concentrations of CMPs, the micro-aliquots of each dilution of suspended CMPs were dried on a surface of hydrophobic membrane and at the optical magnification of 20× the dry residues were than analyzed by measuring the sum of densities. This simple and affordable technique was shown to be considerably more sensitive than spectrophotometry of the aqueous suspensions of CMPs.

Analysis of medical use of carbon adsorbents in China and additional possibilities in this field achieved in Ukraine.

The review is devoted to analysis of the use of carbon sorbents for medicinal purposes in China and description of some innovative technologies in this field in Ukraine. The review underlines the presence of common roots of sorption therapy development in these two countries determined by pioneer works of Prof. T.M.S. Chang, created to the concept of artificial cells. High level of works of Chinese scientists on sorption purification of blood and combined extracorporeal methods has been mentioned. At the same time, by author's opinion, two other methods of sorption therapy, namely enterosorption and sorption therapy of wounds and burns, has not been properly developed in China. In the review, there are also described the essential results of Ukrainian scientists in the field of blood purification from protein-bound toxins and other harmful compounds what is important for treatment of many serious human pathologies, and also the important data on the use of oral sorbents and dressings from activated carbon materials, which could be considered as a useful addition to achievements of Chinese scientists in the field of the development and use of sorbents for medicinal purposes.

Heparin-cellulose-charcoal composites for drug detoxification prepared using room temperature ionic liquids.

We report novel heparin-cellulose-charcoal composites prepared using room temperature ionic liquids (RTILs) to enhance the biocompatibility and blood compatibility of activated charcoal beads while decreasing the size of their active pores.

High-porosity activated carbon as a possible matrix for native DNA and dextran-sulfate immobilization.

In this study, specific and nonspecific activity of calf thymus DNA and Dextran-Sulfate (DS)-containing synthetic carbonic adsorbents (0.7-7mg of each ligands per 1 cm3 of activated carbonic beads, 0.3-0.6mm diameter, bulk density gamma=0.1-0.2g/cm3) have been compared in stir-bath and micro-column in vitro tests. DS coating as well as DNA coating does not demonstrate deep influence on the unspecific adsorptive activity of carbonic matrix toward creatinine, vitamin B12, and unconjugated bilirubin. No essential difference has been found in the specific activity of DNA and DS containing adsorbents toward anti-ds- and anti-ss-DNA-antibodies, as well as antibodies against DNA-protein complexes (anti-DNP-antibodies): in both cases the percentage of decrease of appropriate antibody concentration varied between 35 and 51% for single-pass microcolumn experiments with moderate enhancement of extraction efficacy (up to 60-75%) due to additional recirculation (2 h) or preliminary plasma dilution in 2-5 times. In the micro-column experiments with the proinflammatory cytokines DNA or DS-coating did not diminish TNF-alpha, IL-1beta, and IL-6 adsorption from 3% BSA solution, but even improves to some extent its removal compared with uncoated matrix.

Extraction of uraemic toxins with activated carbon restores the functional properties of albumin.

BACKGROUND: Previous work has demonstrated that a partial normalization of the conformation of albumin from uraemic plasma and a substantial restoration of its binding abilities can be achieved by extraction with activated charcoal. This is best achieved at pH 3, but exposure of whole plasma to this low pH leads to the loss of some essential components. METHODS: The melting curves and ligand-binding abilities of uraemic albumin have been investigated after extraction with a new generation of activated carbon at three pH values (7.2, 3.0 and 5.08). RESULTS: Albumin isolated from uraemic plasma had a characteristically increased melting temperature because of bound ligands. Extraction of uraemic plasma at pH 7.2, 5.08 and 3.0 induced low-temperature shifts of albumin thermo-adsorption maximum T1 of 1.4, 3.8, 2.4 degrees C and T2 of 0.8, 3.9 and 1.2 degrees C, respectively. Flow microcalorimetry data demonstrated a decrease in the ability of uraemic albumin to bind octanoate, phenol red, salicylic acid, warfarin and diazepam. Purification of uraemic plasma at pH 5.08 completely restored the binding affinity of albumin for all the marker ligands. CONCLUSIONS: Highly efficient activated carbons, with clinically feasible acidification of plasma, can remove strongly albumin-bound uraemic toxins. Investigation of the melting curve of the isolated albumin is a new biophysical way to monitor both its molecular condition and the extent of removal of protein-bound toxins by dialysis. The melting curve provides new qualitative and quantitative information about albumin in an analogous way to an electrocardiogram and the heart.

Albumin, bilirubin, and activated carbon: new edges of an old triangle.

The problem of interaction of human serum albumin (HSA), unconjugated bilirubin (UB) and high porosity activated HSGD carbons is investigated in this study. The decrease of UB to HSA molecular ratio by more than 300 times was demonstrated while the batch experiments in HSA-UB admixtures after contact with HSGD. HSGD carbons express extremely high activity for the removal of UB from HSA containing solutions (more than 100 mg of UB per 1 g of activated carbon). Ex-tempore albumin-coating of carbon surface decreases adsorbent capacity by bilirubin on 21%. At the same time ex-tempore albumin-coating of HSGD carbon surface as well as blood citratization prevent platelet and leukocytes loss and clotting inside of the column. Pharmacopoeia solution of HSA containing acetyl-tryptophan or octanoate used for albumin-coating of HSGD adsorbents, becomes ligand-free and rather more active in complexing with protein-bound substances. Combination of albumin-coated HSGD carbon as haemosorbent with HSA ligand-free solution as a transfusion media seems a new prospective modality of the extracorporeal removal of protein-bound toxins.

Effect of protein-bound uraemic toxins on the thermodynamic characteristics of human albumin.

The ability of albumin to bind drugs and other lipophilic organic acids is decreased in chronic renal failure by the accumulation of albumin-bound uraemic toxins such as hippuric acid, indoxyl sulphate and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF). This furan acid is the most highly bound and is not removed by haemodialysis. The inhibitory effects of these three uraemic toxins on the interaction of three marker ligands sodium octanoate (for medium chain fatty acids), salicylic acid and phenol red (bilirubin site/site I) with albumin have been investigated by differential scanning microcalorimetry and flow microcalorimetry. CMPF was the most potent inhibitor and its binding site coincided with that of bilirubin (site I). Indoxyl sulphate binds to the site for medium-chain fatty acids and tryptophan (site II) and hippuric acid, the weakest inhibitor, inhibited binding to the salicylic acid site.