Hemolysis study, blood

Bovine aortic endothelial cells and vascular smooth muscle cells exposed to OCL worm micelles in PBS with a dose of S mg/ml showed no ill-effects for up to 5 days. OCL worm micelles and their degradation product, 6-hydroxycaproic acid are non-toxic and compatible with cultured cells. Incubating OCL worm micelles with whole blood for two days at 37°C shows that they don t stick to red blood cells (RBC) and remains suspended in plasma and retains their flexibility. Also, hemolysis study on OCL worm micelles (lOmg/ml) shows negligible hemolytic activity (< 1%). (27)... 

Hydroxyurea reduced the frequency of hospitalizations and the incidences of pain, acute chest syndrome, and blood transfusions by almost 50% in a landmark trial in adult SCD patients with moderate to severe disease. Hemoglobin and HbF concentrations increased, and hemolysis decreased.22 A follow-up study demonstrated a 40% reduction in mortality over a 9-year period in patients continuing to receive hydroxyurea.23 Not all patients responded equally, so hydroxyurea may not be the answer for all patients. 

Hereditary deficiency of phosphoglycerate kinase (PGK) is associated with hereditary hemolytic anemia and often with central nervous system dysfunction and/or myopathy. The first case, reported by Kraus et al. (K24), is a heterozygous female, and the results are not so clear. The second family, reported by Valentine et al. (V3), is a large Chinese family, whose pedigree study indicates that PGK deficiency is compatible with X-linked inheritance. To date, 22 families have been reported (04, T25, Y3). Nine of these have manifested both symptoms five have shown only hemolysis seven have shown the central nervous system dysfunction and/or myopathy but without hemolysis and one case, PGK Munchen, is without clinical symptoms (F5). PGK II is an electrophoretic variant found in New Guinea populations (Y2). Red blood cell enzyme activity, specific activity, and the kinetic properties of this polymorphic variant are normal. 

The photodynamic effect on red blood cells of the /xara-tetraglucosyl-porphyrin 31a and its analogous with the sugar unit in orto position has also been analysed. Considering the possibility of the photosensitiser causing hemolysis, this study became crucial.29 The two symmetric derivatives have proved to be ineffective in these cells. However, the asymmetric derivatives 49B and 50B are phototoxic and changes in hematological parameters were observed.29... 

Brydon and Roberts- added hemolyzed blood to unhemolyzed plasma, analyzed the specimens for a variety of constituents and then compared the values with those in the unhemolyzed plasma (B28). The following procedures were considered unaffected by hemolysis (up to 1 g/100 ml hemoglobin) urea (diacetyl monoxime) carbon dioxide content (phe-nolphthalein complex) iron binding capacity cholesterol (ferric chloride) creatinine (alkaline picrate) uric acid (phosphotungstate reduction) alkaline phosphatase (4-nitrophenyl phosphate) 5 -nucleotidase (adenosine monophosphate-nickel) and tartrate-labile acid phosphatase (phenyl phosphate). In Table 2 are shown those assays where increases were observed. The hemolysis used in these studies was equivalent to that produced by the breakdown of about 15 X 10 erythrocytes. In the bromocresol green albumin method it has been reported that for every 100 mg of hemoglobin/100 ml serum, the apparent albumin concentration is increased by 100 mg/100 ml (D12). Hemolysis releases some amino acids, such as histidine, into the plasma (Alb). 

Inhibition of immune hemolysis by berberine was described by Tanaka (505). Subcutaneous or intravenous injections of berberine either in single doses or repeatedly did not affect the number of erythrocytes, leukocytes, and the hemoglobin level of intact rabbits (506). In rabbits, with anemia induced by phenylhydrazine and toluenedia-mine, berberine had an antianemic effect. Hasegawa and Tanaka (507) did not observe any effect of berberine on the production of plasma cells. It decreased the anticoagulant action of heparin in dog and human blood in vitro (508). Morthland (509) carried out a spectrophotometric study of the interaction of nucleic acids with aminoacridine or with other basic stains including berberine. 

The major problem in some patients [20% in one study (267)] treated with elliptinium is the development of antielliptinium antibodies (267-270). When these antibodies reach a certain concentration, the red blood cells rupture, causing anemia. This hemolysis is more frequent in patients treated weekly with 5 than in those who are treated every 2-4 weeks (277). Provided the antibody titer in patients is monitored, the onset of hemolysis can be prevented (268). In addition to elliptinium, several other ellipticine derivatives and analogs react with this specific antibody (420, 463-465), whereas the oxazolopyridocarbazole 466 (incorrect structure given in Ref. 268), 9-methoxyellipticine (2), and 9-bromoellipticine do not (268). 

These in vitro cytotoxicity studies are not indicative of in vivo toxicity but rather provide a method to classify the CDs for their potential to destabilize or disrupt cellular membranes. In fact, when whole blood is used instead of erythrocytes for the hemolysis tests, the cytotoxicity of the CDs is diminished 10-fold by the presence of hydrophobic serum components. Thus, the membrane damaging effects of the CDs are observed in vivo only under situations of high concentrations. 

---