Erythrocytes response

This acetone-ether-insoluble portion when administered to four patients in a daily amoimt of 3.4 mg. in addition to 6.4 mg. of the previously mentioned accessory factors, gave on the 10th day an average erythrocyte response of from 1.8 million R.B.C. per cmm. to 2.5 million R.B.C. per cmm. with appropriate reticulocyte response (62). 

In the absence of the three accessory factors, the effect of either fraction E or H alone upon erythrocyte production was moderate. When fractions A, C and F were administered as well, a satisfactory erythrocyte response was obtained. Data taken from their paper illustrating this point are shown in Fig. 1. The administration of a combination of primary and accessory factors resulted in a rate of erythrocyte production closely approximating that produced by the intramuscular administration of an amount of commercial liver extract containing equivalent quantities of the primary and accessory factors. 

The erythrocyte response following the administration of large amounts of the primary factor (H) without the three accessory factors was not as great as the average response to smaller amounts of the primary factor when given together with the accessory factors. This is shown in Fig. 1. 

Their evidence for the importance of fraction C was based on the following results. The continuous administration, over a ten day pmod, of primary factor, as fraction E, together with fraction A but with minimal amounts of fraction C (fraction E contained sufficient fraction F), induced only slight reticulocyte and erythrocyte responses. An increase in the amount of fraction C, however, was followed by a satisfactory blood response as seen in Fig. 2. 

Although it proved inactive in two other cases, intramuscular administration of heparin in one case effected an erythrocyte response, from an initial level of 2.6 millions to 3.9 millions in a four week period. There was no indication of a reticulocyte response at any time during treatment. As Aleksandrowicz and Gabryelski admit, the therapeutic value of anti-prothrombin is not supported by this single case. 

In the absence of a more satisfactory basis of comparison, a few of the preparations may be compared in terms of erythrocyte response elicited by definite quantities of different products (see Fig. 3). Inasmuch as the size of response varies with the initial red blood cell level, an attempt has been made to compare cases in which the initial erythrocyte levels were about 1.2 to 1.8 million. Responses reported by Murphy (92) and Hartfall... 

Plasmodium vivax, responsible for the most prevalent form of malaria (benign tertian), has an incubation period of 8—27 days (14 average). A variety seen in northern and northeastern Europe has an incubation period as long as 8—10 months. The disease can cause splenic mpture and anemia. Relapses (renewed manifestations of erythrocytic infection) can occur with this type of malaria. Overall, P. vivax is stiU susceptible to chloroquine however, resistant strains have been reported from Papua New Guinea and parts of Indonesia. Plasmodium malariae the cause of quartan malaria, has an incubation period of 15—30 days and its asexual cycle is 72 hours. This mildest form of malaria can cause nephritis in addition to the usual symptoms. It is a nonrelapsing type of malaria but the ted blood ceU infection can last for many years. No resistance to chloroquine by this plasmodium has been reported. Plasmodium ovale responsible for ovale tertian malaria, has an incubation period of 9—17 days (15 average). Relapses can occur in people infected with this plasmodium. No chloroquine resistance has been reported for this parasite. 

Erythrocyte Entrapment of Enzymes. Erythrocytes have been used as carriers for therapeutic enzymes in the treatment of inborn errors (249). Exogenous enzymes encapsulated in erythrocytes may be useful both for dehvery of a given enzyme to the site of its intended function and for the degradation of pathologically elevated, diffusible substances in the plasma. In the use of this approach, it is important to determine that the enzyme is completely internalized without adsorption to the erythrocyte membrane. Since exposed protein on the erythrocyte surface may ehcit an immune response following repeated sensitization with enzyme loaded erythrocytes, an immunologic assessment of each potential system in animal models is required prior to human trials (250). 

Proteins that can flip phospholipids from one side of a bilayer to the other have also been identified in several tissues (Figure 9.11). Called flippases, these proteins reduce the half-time for phospholipid movement across a membrane from 10 days or more to a few minutes or less. Some of these systems may operate passively, with no required input of energy, but passive transport alone cannot establish or maintain asymmetric transverse lipid distributions. However, rapid phospholipid movement from one monolayer to the other occurs in an ATP-dependent manner in erythrocytes. Energy-dependent lipid flippase activity may be responsible for the creation and maintenance of transverse lipid asymmetries. 

Several cytokines are in clinical use that support immune responses, such as IL-2, DFNs, or colony-stimulating factors. IL-2 supports the proliferation and effector ftmction of T-lymphocytes in immune compromised patients such as after prolonged dialysis or HIV infection. IFNs support antiviral responses or antitumoral activities of phagocytes, NK cells, and cytotoxic T-lymphocytes. Colony-stimulatory factors enforce the formation of mature blood cells from progenitor cells, e.g., after chemo- or radiotherapy (G-CSF to generate neutrophils, TPO to generate platelets, EPO to generate erythrocytes). 

A dose-response relationship was noted in dogs exposed to 0.03, 0.3, or 3.0 mg/kg/day methyl parathion in the diet for 13 weeks (Daly 1989). Significant reductions in erythrocyte cholinesterase activity (20-23%) and cholinesterase activity in the pons and cerebellum of the brain (43-54%) occurred in dogs... 

In starvation, glucose must be ptovided for the brain and erythrocytes initially, this is supphed from hver glycogen reserves. To spare glucose, muscle and other tissues reduce glucose uptake in response to lowered insuhn secretion they also oxidize fatty acids and ketone bodies preferentially to glucose. 

Many microorganisms minimize the effects of the host s defence system against them by mimicking the antigenic stmcture of the host tissne. The eventual immunological response of the host to infection then leads to the autoimmune destmction of itself. Thus, infections with Mycoplasma pneumoniae can lead to production of antibody against normal Group 0 erythrocytes with concomitant haemolytic anaemia. 

Higuchi, M., Cartier, L.J., Chen, M. and HoUoszy, J.O. (1985). Superoxide dismutase and catalase in skeletal muscle adaptive response to exercise. J. Gerontol. 40, 281-286. Hunter, M.I.S., Brzeski, M.S. and de Vane, P.J. (1981). Superoxide dismutase, glutathione peroxidase and thiobarbi-turic acid-reactive compounds in erythrocytes in Duchenne muscular dystrophy. Clin. Chim. Acta 115, 93-98. 

Hepatic reperfusion injury is not a phenomenon connected solely to liver transplantation but also to situations of prolonged hypoperfusion of the host s own liver. Examples of this occurrence are hypovolemic shock and acute cardiovascular injur) (heart attack). As a result of such cessation and then reintroduction of blood flow, the liver is damaged such that centrilobular necrosis occurs and elevated levels of liver enzymes in the serum can be detected. Particularly because of the involvement of other organs, the interpretation of the role of free radicals in ischaemic hepatitis from this clinical data is very difficult. The involvement of free radicals in the overall phenomenon of hypovolemic shock has been discussed recently by Redl et al. (1993). More specifically. Poll (1993) has reported preliminary data on markers of free-radical production during ischaemic hepatitis. These markers mostly concerned indices of lipid peroxidation in the serum and also in the erythrocytes of affected subjects, and a correlation was seen with the extent of liver injury. The mechanisms of free-radical damage in this model will be difficult to determine in the clinical setting, but the similarity to the situation with transplanted liver surest that the above discussion of the role of XO activation, Kupffer cell activation and induction of an acute inflammatory response would be also relevant here. It will be important to establish whether oxidative stress is important in the pathogenesis of ischaemic hepatitis and in the problems of liver transplantation discussed above, since it would surest that antioxidant therapy could be of real benefit. 

Organophosphate insecticides also inhibit RBC-ACHE and PCHE. Inhibition of ACHE in erythrocytes is assumed to mirror inhibition of ACHE in the nervous system, which is the receptor of the toxic action, to some extent. Therefore, measurements of RBC-ACHE and PCHE are used for biological monitoring of exposure to OP insecticides (Maroni, 1986). Inhibitions of RBC-ACHE and PCHE activities are correlated with intensity and duration of exposure, although at different levels for each OP compound. Blood ACHE, being the same molecular target as that responsible for acute toxicity in the nervous system, is a true indicator of effect, while PCHE can only be used as an indicator of exposure. 

Dose-Response Curve for Erythrocyte Protoporphyrin (EP) as a Function of Blood Level in Subpopulations... 

Effects at even lower external and internal exposure levels were reported by Hayashi (1983). Lead acetate at 0.7 mg lead/kg/day in the drinking water of rats for the first 18 or 21 days of pregnancy resulted in decreased ALAD activity in the fetal and maternal erythrocytes and increased ALAD activity in fetal but not maternal liver. Fetal, but not maternal, hematocrits and hemoglobin levels were decreased in the group treated for 21 days. Fetal PbB levels were 27 pg/dL and 19 pg/dL in the 18-day and the 21-day treated groups, respectively. Maternal PbB levels were approximately 4 pg/dL in treated and control groups. The study is limited by the use of one dose level, which precluded assessment of dose response. 

Hammond PB, Bomschein RL, Succop P. 1985. Dose-effect and dose-response relationships of blood lead to erythrocytic protoporphyrin in young children. In Bomschein RL, Rabinowitz MB, eds. The Second International Conference on Prospective Studies of Lead, Cincinnati, OH April, 1984. Environ Res 38 187-196. 

Marcus AH, Schwartz J. 1987. Dose-response curves for erythrocyte protoporphyrin vs blood lead Effects of iron status. Environ Res 44 221-227. 

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