Hematopoietic systems

Sodium nitroprusside, Na2[Fe(CN)5NO] 2H20 (99), is the only clinically used metal complex of nitric oxide (501). It is often used to lower 

The therapeutic effects of sodium nitroprusside depend on release of nitric oxide which relaxes vascular muscle. Sodium nitroprusside is best formulated as a nitrosonium (NO+) complex. Its in vivo activation is probably achieved by reduction to [Fe(CN)5NO]3, which then releases cyanide to give [Fe(CN)4NO]2, which in turn releases nitric oxide and additional CN to yield aquated Fe(II) species and [Fe(CN)6]4 (502). There are problems associated with its use, namely reduced activity due to photolysis (501) and its oxidative breakdown due to the action of an activated immune system (503), both of which release cyanide from the low-spin d6 iron complex. 

There is interest in the possible use of other metal nitrosyl complexes as vasodilators, but from the series KJM(CN)6NO] where M = V, Cr, Mn, and Co (n = 3) or M = Mo (n = 4) neither the Cr nor the Mn complexes exhibit any hypotensive action (504). Iron-sulfur-nitrosyl clusters such as [Fe4S4(NO)4] are active, and their effects can be potentiated by visible light (505). 

Complex 101 has been shown to reverse the poor response of the artery to vasoconstrictor drugs (508), which is a major clinical problem in the treatment of patients with septic shock. The excessive production of NO appears to be a major contributory factor not only in 

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D. Agents which act on the blood or hematopoietic system Decreases hemoglobin function deprive body tissues of oxygen ... 

Milsom MD, Fairbaim LJ (2004) Protection and selection for gene therapy in the hematopoietic system, J Gene Med 6 133-146... 

Szarfman A, Talarico L, Levine JG. Analysis and risk assessment of hematological data from clinical trials toxicology of the hematopoietic system. In Sipes IG, McQueen CA, Gandolfi AJ, editors. Comprehensive toxicology. Vol. 4. New York Elsevier Science, 1997, p. 363-79. 

The properties and functions of chemokines were initially elucidated based on then-effects on the hematopoietic system, and their functions in the nervous system were not originally appreciated. Interestingly, the very first observation indicating that... 

Hematological Effects. The effects of lead on the hematopoietic system have been well documented. These effects, which are seen in both humans and animals, include increased urinary porphyrins, coproporphyrins, ALA, EP, FEP, ZPP, and anemia. The process of heme biosynthesis is outlined in Figure 2-10. Lead interferes with heme biosynthesis by altering the activity of three enzymes ALAS,... 

The impairment of heme synthesis by lead has a far-ranging impact not limited to the hematopoietic system. EPA (1986a) provided an overview of the known and potential consequences of the reduction of heme synthesis as shown in Figure 2-11. Well documented effects are indicated by solid arrows, and effects considered to be plausible further consequences of the impairment of heme synthesis are indicated by dashed arrows. Additional discussion is provided in the following sections on renal and neurological effects. More detailed information on the exposure levels or blood lead levels at which these impacts may be experienced was provided in Section 2.2 and the relevance to human health is discussed in Section 2.5. 

Lead has been shown to affect virtually every organ and/or system in the body in both humans and animals (see Figure 2-11). The most sensitive target organs of lead appear to be the nervous system (particularly in children), the hematopoietic system, and the cardiovascular system. There is evidence in... 

Dietary copper also appears to be antagonistic to the adverse effects of lead on the hematopoietic system, growth depression, and tissue hypertrophy (Klauder and Peterini 1975). The reduction in uptake of lead and decrease of lead-induced ALAD inhibition upon administration of copper may be achieved through a competition between the two metals for binding to proteins (Underwood 1977). 

Gaspard, K.J., Blood cells and the hematopoietic system, in Pathophysiology Concepts of Altered Health States, 5th ed., Porth, C.P., Ed., Lippincott, Philadelphia, 1998. 

FIGURE 2 9-3 Intravenous administration of stem cells can reconstitute the blood forming system, and may provide cells to other tissues. In classical studies, Till and McCulloch administered dissociated bone marrow cells in the tail vein of lethally irradiated mice and found that the grafted cells repopulated the hematopoietic system and allowed the animals to survive. More recent studies suggest that blood cells also travel to sites of injury, where they may give rise to non-blood-tissue progeny. 

The overall effect of Li+ on the hematopoietic system is of stimulation of the immune system. Not surprisingly then, Li+ is reported to exacerbate the activity of a number of autoimmune diseases, such as psoriasis [212] and rheumatoid arthritis [213], and to result in the production of autoantibodies in some patients [214]. However, there is no evidence that Li+ s stimulation of the immune system leads to any reduction in the occurrence of viral or bacterial infections in patients on Li+ therapy. 

The literature emphasizes that arsenic metabolism and toxicity vary greatly between species and that its effects are significantly altered by numerous physical, chemical, and biological modifiers. Adverse health effects, for example, may involve respiratory, gastrointestinal, cardiovascular, and hematopoietic systems, and may range from reversible effects to cancer and death, depending partly on the physical and chemical forms of arsenic tested, the route of administration, and the dose. 

Rollins-Smith, L.A., Hopkins, B.D., and Reinert, L.K. An amphibian model to test the effects of xenobiotic chemicals on development of the hematopoietic system, Environ. Toxicol. Chem., 23, 2863, 2004. 

Thyroid gland Hematopoietic system Adrenal gland Pancreas Seminal vesicle Urinary tract Lymphatic system... 

Hematologic Effects. Effects of 1,2-dibromoethane on the hematopoietic system of humans exposed by inhalation, oral, or dermal routes have not been described. Results of animal studies are equivocal except that, based on a study in rats, individuals taking disulfiram for alcoholism might be a susceptible human subpopulation at higher risk for adverse hematopoietic effects (Wong et al. 1982) (See Sections 2.6 and 2.7). 

Hematological Effects. Intermediate and chronic inhalation exposure of humans to mixtures of heptachlor, chlordane, and other chemicals has been associated with leukemia and aplastic and hemolytic anemias. These exposures were either occupational or followed the use of termiticides in homes. These exposures were probably primarily inhalation combined with dermal. There are oral animal studies that confirm that the hematopoietic system, specifically the white cells, can be affected by heptachlor exposure. Rats fed 0.5 mg/kg/day heptachlor in the diet showed a statistically significant increase in total white blood count (Enan et al. 1982). It appears that although the hematopoietic system is not a primary target for heptachlor or heptachlor epoxide, it can be measurably affected. 

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