Erythrocyte polyamine

Tsukamoto T, Kinoshita H, Hirohashi K et al. (1999) Human erythrocyte polyamine levels after portal vein embolization. Hepatogastroenterology 46 3178-3183... 

Ethambutol is a synthetic agent and not related to any of the other tuberculostatics. Its mechanism of action is not well understood but in actively dividing mycobacteria it appears to be an inhibitor of mycobacterial RNA synthesis. It also has effects on bacterial phosphate metabolism and on polyamine synthesis. It is an bacteriostatic agent and its main function in combination therapy is to delay the occurrence of resistance, mainly against isoniazid and rifampicin. It is well absorbed after oral administration. It is widely distributed, except to the CNS. Protein binding is about 20-30%. It is mainly excreted unchanged in the bile and urine with an elimination half-life of 3 h. Ethambutol is concentrated in erythrocytes and thus provides a depot for continuous release. 

In this connection, it is to be noted that polyamine-modified po y(HEMA) surfaces exhibit surprisingly reduced interaction with blood proteins and cells (e.g. erythrocyte, platelet, lymphocyte etc.), as will be discussed in Sects. 4.3 and 4.4. The present author considers that there are probably closely related mechanisms between the suppressing effect of the poly(DIPAM) or (Methacrol)-modi-fied SPU and that of the polyamine-modified poly(HEMA) surfaces, with regard to their mode of interaction with the biological elements. 

Although its mode of action is uncertain, two mechanisms, one involving interference with the production and/or utilization of polyamines and the other preventing the entry of inositol into the erythrocyte that contains the parasite, have been proposed. It is a compound with low safety margin since administration of as low as 10 mg/kg bw to cattle can cause death. By now, its withdrawal periods in edible animal products are under review by the licensing authorities and, in some cases, a 90-day withdrawal period may be required (4). 

Assaraf, Y. G., Golenser, J., Spira, D. T., and Bachrach, U. (1984). Polyamine levels and the activity of their biosynthetic enzymes in human erythrocytes infected with the malarial parasite, Plasmodium falciparum. Biochem. ]. 222, 815-819. 

Urinary polyamines are also extensively studied as biochemical markers of cancer. Measurement of polyamines in erythrocytes also appears to be the most promising area for assessing their levels in circulation. The majority of the circulating polyamines are associated with erythrocytes leading to the hypothesis that they may serve as passive carriers from sites of conjugation, catabolism, excretion, and reuptake. 

The most commonly applied methods for the analysis of polyamines in erythrocytes make use of amino acid analyzers and HPLC techniques. A capillary gas chromatographic method with nitrogen-phosphorous detection was applied to the simultaneous determination of 1,3-diaminopropane, putrescine, cadaverine (Cad), spermidine (Sd), and spermine (Sp) in human erythrocytes. Blood samples, collected by venipuncture into EDTA containing Venoject tubes, were subjected to the removal of plasma by centrifugation and erythrocytes were washed three times with two volumes of 0.9% NaCl. The stability of polyamines in erythrocyte suspensions was also investigated. Quantification of polyamines was done by comparing the peak-area ratio of each analyte and its internal standard with that of the standard. The polyamine samples were eluted with 0.1 M hydrochloric acid solutions. The eluate was evaporated to dryness at 120°C under a stream of air and 200 each of acetonitrile and heptafluorobutyric anhydride were added. The isolation of derivatives... 

Vanderberg, G. A., Kingma, A. W., and Muskiet, E. A. J., Determination of polyamines in human erythrocytes by capillary gas chromatography with nitrogen-phosphorous detection, J. Chromatogr.,... 

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