Hemolysis properties

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. 

These specific substances or blood group factors are detected by their property of inhibiting agglutinin reactions between human erythrocytes and heterologous human sera. This is the so-called isoagglutinin test which can detect the factors in dilutions of more than 1 part in 10 million. An even more sensitive but less specific test is their power to inhibit hemolysis of sheep s erythrocytes by the serum of rabbits immunized with certain human corpuscles. 

Most of the early work on membranes was based on experiments with erythrocytes. These cells were first described by Swammerdam in 1658 with a more detailed account being given by van Leeuwenhoek (1673). The existence of a cell (plasma) membrane with properties distinct from those of protoplasm followed from the work of Hamburger (1898) who showed that when placed in an isotonic solution of sodium chloride, erythrocytes behaved as osmometers with a semipermeable membrane. Hemolysis became a convenient indication of the penetration of solutes and water into the cell. From 1900 until the early 1960s studies on cell membranes fell into two main categories increasingly sophisticated kinetic analyses of solute translocation, and rather less satisfactory examinations of membrane composition and organization. 

Copper(II) sulfate is toxic to humans by ingestion and other routes of exposure. Symptoms of ingestion include gastritis, diarrhea, nausea, vomiting, kidney damage and hemolysis (Lewis (Sr.), R. N. 1996. Sax s Dangerous Properties of Industrial Materials, 9th ed. New York Van Nostrand Reinhold). LDsooral (rat) 300 mg/kg... 

Vitamin E may be indicated in some rare forms of anemia such as macrocytic, megaloblastic anemia observed in children with severe malnutrition and the hemolytic anemia seen in premature infants on a diet rich in polyunsaturated fatty acids. Also anemia s in malabsorption syndromes have shown to be responsive to vitamin E treatment. Finally, hemolysis in patients with the acanthocytosis syndrome, a rare genetic disorder where there is a lack of plasma jS-lipoprotein and consequently no circulating alpha tocopherol, responds to vitamin E treatment. In neonates requiring oxygen therapy vitamin E has been used for its antioxidant properties to prevent the development retrolental fibroplasia. It should be noted that high dose vitamin E supplements are associated with an increased risk in allcause mortality. 

On the other hand toluene (4) and 5-methoxy-indole (5) would not be considered very similar from a conventional point of view, yet their hemolytic activity is the same (logl/C = 1.93, where C is the minimal molar concentration which causes 100% hemolysis in rabbit erythrocytes l)). Obviously, topological similarity or dissimilarily is not always a factor which is relevant for biological activity. In the present example the relevant feature is a physicochemical property of the compounds, i.e. lipophilicity as expressed by the octanol/water partition coefficient... 

The red tide alga Prymnesium parvum poses a serious threat to fish farming. Prymnesin-2 (184) (CggHnsC NC ), the major toxin of the phytoflagellate, shows potent hemolytic and ichthyotoxic properties. The minimum concentration to cause hemolysis of a 1% mouse blood cell suspension and to kill fresh water fish, Tanichthys albonubes, is 3 nM [145]. 

The finding that water-soluble flavonoids could exert their beneficial properties at the hydrophobic portion of the membrane was also observed in in vivo studies and in cells in culture. For example, erythrocytes obtained from animals fed a flavanol- and procyanidin-rich meal showed reduced susceptibility to free-radical-mediated hemolysis [Zhu et al., 2002]. Consistently, we demonstrated that procyanidin hexamers, which interact with membranes but would not be internalized, protected Caco-2 cells from AMVN- and bile-induced oxidation [Erlejman et al., 2006]. When liposomes were preincubated with a series of flavonoids with diverse hydrophobicity, not only hydrophobic flavonoids prevented AMVN-mediated lipid oxidation but also the more hydrophilic ones [Erlejman et al., 2004]. Similarly to what was previously found in liposomes, the protective effects of flavonoids against AMVN-supported oxidation was strongly associated with their capacity to prevent membrane disruption by detergents, supporting the hypothesis of a physical protection of membranes by preventing oxidants to reach fatty acids. 

Impact on PK properties Precipitation Pain/irritation Hemolysis... 

Adhesives used in medical devices are tested for their effect on cells (cytotoxicity), blood constituents (hemolysis), and adjacent tissues, and for overall systemic effect. Several classes of biocompatibility testing exist. Adhesive suppliers, however, generally test to the following guidelines that have been established for toxicological properties and biocompatibility ... 

The accumulation of hydrogen peroxidase affects many intracellular processes and results in hemolysis. These include the cross-linking of membrane proteins hemoglobin denaturation (manifest as Heinz body formation), which in turn affects the physical properties of the erythrocyte and lipid peroxidation, which may affect the cell membrane to cause direct hemolysis (Fig. 11-8). The resultant damage leads to a mixture of intravascular hemolysis and extravascu-lar hemolysis (by which hemolysis occurs in the reticuloendothelial system). In acute hemolytic episodes, the clinical picture is of predominantly intravascular hemolysis, while predominantly extravascular hemolysis is seen in patients with chronic hemolysis. 

Lipophilic compounds, such as the various terpenoids, tend to associate with other hydrophobic molecules in a cell these can be biomembranes or the hydrophobic core of many proteins and of the DNA double helix [10,18,24,25]. In proteins, such hydrophobic and van der Waals interactions can also lead to conformational changes, and thus protein inactivation. A major target for terpenoids, especially saponins, is the biomembrane. Saponins (and, among them, the steroid alkaloids) can change the fluidity of biomembranes, thus reducing their function as a permeation barrier. Saponins can even make cells leaky, and this immediately leads to cell death. This can easily be seen in erythrocytes when they are attacked by saponins these cells burst and release hemoglobin (hemolysis) [1,6,17]. Among alkaloids, steroidal alkaloids (from Solanaceae) and other terpenoids have these properties. 

Such relationships can be useful in designing synthetic membranes having properties similar to natural systems. For example, Equation 4 correlates the change in resistance caused by alcohols on potassium ion permeability of black lipid membrane (BLM) prepared from the lipid of sheep erythrocytes. The rather large negative intercept of Equation 4 indicates that three times the concentration of isolipophilic alcohol is needed to change the resistance of the BLM as is needed to cause hemolysis. Although the two processes are quite different, the role of hydrophobic forces in each can be compared. 

Patients with this abnormality suffer from mild hypochromic anemia with microcytosis and signs of hemolysis a highly characteristic property is the 2- to 3-fold increase in the relative production of Hb-Aa. The Hb-level may vary between 7.5 and 11.5 g/100 ml. Anemia is the most common disturbance followed by hepatomegaly, gall stones, jaundice, splenomegaly, and others (G5). The red blood cell count varies between 5.5 and 7,5 million/mm with mean cell volumes (MCV) of 55-80 and mean cellular hemoglobin concentrations (MCHC) of 25-30%. The peripheral blood film shows hypochromia and microcytosis,... 

The most common adverse effects of fusidic acid are minor and are related to the gastrointestinal tract (discomfort, diarrhea). Rare adverse events include granulocytopenia, thrombocytopenia, venous spasm, and skin reactions (4). Fusidic acid has detergent properties and can cause hemolysis when injected intravenously or can induce tissue damage when given intramuscularly. However, its systemic toxicity is relatively low. 

Hemolysis procedures are described in ASTM F756-93 Standard Practice for Assessment of Hemolytic Properties of Materials and ASTM F1841-97 Standard Practice for Assessment of Hemolysis in Continuous Flow Blood Pumps . The presence of... 

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