Blood elements

There are undifferentiated stem cells of the blood elements in the bone marrow that differentiate and mature into erythrocytes, (red blood cells), thrombocytes (platelets), and white blood cells (leukocytes and lymphocytes). The production of erythrocytes is regulated by a hormone, erythropoietin (see the section on kidney toxicity), that is synthetized and excreted by the kidney. An increase in the number of premature erythrocytes is an indication of stimulation of erythropoiesis, i.e., increased production of erythrocytes in anemia due to continuous bleeding. 

Toxic Effects on the Blood-Forming Tissues Reduced formation of erythrocytes and other elements of blood is an indication of damage to the bone marrow. Chemical compounds toxic to the bone marrow may cause pancytopenia, in which the levels of all elements of blood are reduced. Ionizing radiation, benzene, lindane, chlordane, arsenic, chloramphenicol, trinitrotoluene, gold salts, and phenylbutazone all induce pancytopenia. If the damage to the bone marrow is so severe that the production of blood elements is totally inhibited, the disease state is termed aplastic anemia. In the occupational environment, high concentrations of benzene can cause aplastic anemia. 

Drugs frequently bind to blood elements directly (e.g. penicillin to erythrocytes) and the antibodies to the resultant complex react with, and damage, cells coated with the drug. Viruses, especially those that bud, become associated with the host cell surface antigens with the resultant generation of Tc cells. 

The LC50 in mice was 2236ppm for 10 minutes signs of exposure were irritation of eyes and nose, delayed-onset pulmonary edema, and renal tubular damage with proteinuria, hemamria, and elevated blood urea nitrogen. In other exposed animals, a decrease in the white blood cell count and a depression of all blood elements have also been observed. ... 

Lysis of formed blood elements other than erythrocytes may produce elevations in serum or plasma constituents. Platelet breakdown during blood collection can introduce enzymes into the plasma (Z3). Aldolase activity is very high in platelets (Dl), and elevations of acid phosphatase in myeloproliferative disease are probably the result of platelet lysis (B6). 

Red blood cell labeling inhibition. Tobacco decreased the labeling of blood elements with technetium-99m and plasma proteins. This effect possibly resulted from either a direct or an indirect effect (reactive oxygen species [ROS]) of tobacco by oxidation of the stannous ion, possible damages caused in plasma membrane and/or possible chelating action on the stannous and/or pertechnetate ions . 

TABLE 6 6. Evidence of intracellular calcium in blood elements of bipolar patients... 

Derived growth factors—cytokines that regulate proliferation of other blood elements such as platelets (e.g., platelet-derived growth factor [PDGF])... 

The problems encountered most frequently with sulfonamide drugs include gastrointestinal distress, increased skin sensitivity to ultraviolet light, and allergic reactions. Serious disturbances in the formed blood elements, including blood dyscrasias such as agranulocytosis and hemolytic anemia, may also occur during systemic sulfonamide therapy. 

In case a concentration ratio (blood/plasma) is distinctly higher than the hematocrit value, this could indicate a binding of the drug or its metabolites to formed blood elements. 

Investigate the time course of radioactivity concentrations in blood and plasma with the aim to getting information about the absorption process, the AUC, Cmax and the elimination half-life of radioactivity in blood and plasma. Possibly indices for enterohepatic cycle or for metabolites with very different volume of distribution from the original compound may be found. An estimate of the absorption rate comparing dose normalized AUCs after iv and oral (or any other) administration can be done and a major binding to formed blood elements can be noticeable by comparison of blood and plasma concentrations. 

Since all plasma radioactivity concentrations are distinctly higher than the corresponding blood values, there is no indication for a major binding of radioactivity to formed blood elements in this study. 

Hematological Effects. Both human and animal studies have shown that benzene exerts toxic effects on various parts of the hematological system. All the major types of blood cells are susceptible (erythrocytes, leukocytes, and platelets). In the less severe cases of toxicity, specific deficiencies occur in individual types of blood elements. A more severe effect occurs when there is hypoplasia of the bone marrow, or hypercellular marrow exhibiting ineffective hematopoiesis so that all types of blood cells are found in reduced numbers. This is known as pancytopenia. A biphasic response (i.e., a hyperplastic effect in addition to destruction of the bone marrow cells) has been observed (Aksoy et al. 1972, 1974 Doskin... 

Malignant tumor cells in the blood stream interaction with blood elements and platelet aggregation... 

Platelets are contractile blood elements with a specialized task in the arrest of bleeding. The fundamental mechanisms of this specific hmction involve adhesion, aggregation, internal contraction and secretion. Furthermore, the phospholipids present in the platelet membranes play a key role in the development of coagulation mechanisms. 

Activation of platelets by contact with artificial surfaces is a key event in the thromboembolic ccanplicadcxis of prosthetic devices in omtact with the blood (11,12), but the exact mechanism of these events is n(rt fidly understood. It is known that a film of plasma protein adsrabs on artificial materials exposed to blood and that this event proceeds interaction of the surface with blood cells (12,13). The onnpositicHi of the protein film and the configuration of its molecular constituents must reli to the blood elements information describing the nature of the underlying surface. 

Carmustine is given as a single dose by intravenous injection at l(K) to 200 mg/m. A repeat course is not given until the blood elements return to normal levels, which requires about 6 weeks. 

After administration, vincristine is rapidly distributed to ksues and bound to formed blood elements. Elimination is triphasic, with more than half of the drug cleared within 20 ainulcs. The primary mode of elimination is hepatic extraction with secretion into bile. 

In the normal adult, the marrow is found in the central hollow segment of bones. Hematopoiesis, or the production of the formed blood elements, occurs in the bone marrow. However, in the adult, it is largely restricted to scattered clusters of hemopoietic cells in the proximal epiphyses of the long bones, skull, vertebrae, pelvis, ribs, and sternum. The hematopoietic... 

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