Hemosiderin

what can be done Obviously, the Ideal solution would be a treatment which would allow the bone marrow to make normal amounts of alpha and beta globln chains, thereby correcting the abnormality. Until this becomes possible, however, the next alternative Is to Improve techniques for removing excess Iron from the body tissues or even to chelate and excrete excess Iron before It Is ever deposited In the body. 

Let me now spend a few minutes summarizing the general field of iron chelator development. The best organic chemists for producing effective iron chelators are the microbes ( ). They have been doing It for millions of years, and have developed extremely effective molecules for chelating iron. Dr. Nellands, the expert on bacterial Iron chelators, will be the next speaker. 

It is not particularly effective since it can only form two bonds, while iron utilizes six. At the other extreme is ferrachrome, an absolutely beautiful molecule, which is like a Venus Fly Trap with three hydroxamlc acid groups - one in the back of each of three arms. Once iron goes in, it is held in place very tightly by six bonds. Ferrachrome is one of the most effective iron chelators in nature. 

But neither ferrachrome, which is too complex, nor hada-cldln, which is too simple, are effective in chelating iron from the tissues of animals. The type of molecule that one wants is one which is fairly simple and which has three hydroxamlc acids 

ACS Symposium Series American Chemical Society Washington, DC, 1980. 

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Hemophilia A Hemophilus influenzae Hemorrhage Hemorrhoids Hemosiderin Hemo stats Hemp... 

Hemosiderin is a somewhat ill-defined molecule it appears to be a pardy degraded form of ferritin but still containing iron. It can be detected by histologic stains (eg, Pmssian blue) for iron, and its presence is determined histologically when excessive storage of iron... 

Finally, animal, plant and microbial tissues have been shown to contain the iron storage protein ferritin. The animal protein has been extensively studied, but the mechanism of iron binding has not been completely resolved (29). Animal tissues contain, in addition, a type of granule comprised of iron hydroxide, polysaccharide and protein. The latter, called hemosiderin, may represent a depository of excess iron (30). Interestingly, a protein with properties parallel to those of ferritin has been found in a mold. Here the function of the molecule can be examined with the powerful tools of biochemical genetics (31). 

The answer is b. (Hardman, pp 1324,1668. KatzmigT p 1009J Deferoxamine is the treatment of choice in acute Fe overload when the plasma concentration of Fe exceeds the total Fe binding capacity It has a high affinity for loosely bound Fe in Fe-carrying proteins such as ferritin, hemosiderin, and transferrin. The metal complex is excreted in the urine. 

Further details of the above study were discussed in U.S. EPA (1994). After the last exposure, methemoglobin levels were elevated in a dose-dependent manner 17 ppm, 0% to 2.9% (no different from controls) 45 ppm, 2.2% to 5.4% and 87 ppm, 4.2% to 23%. The animals exposed at 45 and 87 ppm were anemic with decreases in RBC counts, hemoglobin content, MCHb concentration, and hematocrit, and accompanying increases in erythropoietin foci, reticuloendothelial cell hypertrophy, and hemosiderin deposition in the spleen. The animals in the 87-ppm exposure group were judged cyanotic. In the 17-ppm exposure group, effects were limited to mild splenic congestion. 

Hemosiderin binds excess Fe " to prevent escape of free Fe + into the blood where It is toxic. 

Pigments such as melanin and hemosiderin These differ in texture and color from the chromogen but may be difficult in interpretation. However, the negative control will demonstrate their true character, and by using a chromogen of a contrasting color (i.e., AEG stains positive cells a red color), this problem can be minimized. 

This loss is compensated by the alimentation. 70 % of the body iron is contained in hemoglobin. Transferrin ensures the transport of iron, while ferritin and hemosiderin are used for the storage of iron in a non-toxic form ferritin is indeed able to transform the highly toxic Fe(II) in to the less toxic Fe(III). 

The problems to be solved are listed hereafter the first problem is the lack of data concerning the exact proportions of low-molecular weight iron complex, ferritin-bound iron and hemosiderin-bound iron (54). However, transverse NMRD profiles of iron-loaded tissues indicate that the transverse relaxation is essentially caused by ferritin, because of the linearity between I/T2 and Bq, which is a fingerprint of ferritin-induced relaxation. The relaxation properties of hemosiderin are less understood. If the proportion of ferritin and hemosiderin is not the same in all of the studied tissues, the correlation between the relaxation properties and the total iron concentration could be affected. 

Higher nuclearity oxo-lron centers are present in iron storage proteins like ferritin (Ft) and hemosiderin (Hs)(l) as well as in magnetotactic organisms and in the teeth of chitons(2). In the latter two cases magnetite is the predominant phase. In the case of the storage proteins (see Chapter 9), the metallic cores are structurally poorly characterized and numerous questions concerning their formation, structure and functionality remain to... 

Excess iron is incorporated into ferritin and stored in this form in the liver and other organs. The ferritin molecule consists of 24 subunits and has the shape of a hollow sphere (bottom left). It takes up Fe ions, which in the process are oxidized to Fe " and then deposited in the interior of the sphere as fer-rihydrate. Each ferritin molecule is capable of storing several thousand iron ions in this way. In addition to ferritin, there is another storage form, hemosiderin, the function of which is not yet clear. 

As the human body is able to store many minerals, deviations from the daily ration are balanced out over a given period of time. Minerals stored in the body include water, which is distributed throughout the whole body calcium, stored in the form of apatite in the bones (see p. 340) iodine, stored as thyroglobulin in the thyroid and iron, stored in the form of ferritin and hemosiderin in the bone marrow, spleen, and liver (see p. 286). The storage site for many trace elements is the liver. In many cases, the metabolism of minerals is regulated by hormones—for example, the uptake and excretion of H2O, Na, ... 

In intermediate-duration studies, spleen enlargement occurred in male and female rats treated with approximately 1 mg/kg/day 1,3-DNB in the drinking water for 16 weeks (Cody et al. 1981). Similar results were reported in rats administered 1.5 mg/kg/day 1,3-DNB by gavage for 12 weeks (Linder et al. 1986). Treatment of rats with doses of about 12-14 mg/kg/day 1,3-DNB in the drinking water for 8 weeks induced hemosiderin deposits in the spleen and spleen atrophy and fibrosis (Cody et al. 

Iron occurs in every mammalian cell and is vital for life processes. It is bound to various proteins and found in blood and tissues. The iron-porphyrin or heme proteins include hemoglobin, myoglobin and various heme enzymes, such as cytochromes and peroxidases. Also, it occurs in non heme compounds, such as ferritin, siderophilin, and hemosiderin. Hemoglobin, found in the red blood cells, is responsible for transport of oxygen to the tissue cells and constitutes about two-thirds (mass) of all iron present in the human body. An adult human may contain about 4 to 6 grams of iron. 

Exposure of rats to carbon tetrachloride (up to 160 mg/kg/day for 10 days) by gavage did not alter the primary antibody response to sheep red blood cells, lymphoproliferative responses to mitogen or mixed leukocytes, natural killer cell activity, or cytotoxic T lymphocyte responses also, spleen and thymus weights were comparable to controls (Smialowicz et al. 1991). In rats exposed twice weekly for 4-12 weeks to 3,688 mg/kg/day, there was histologic evidence of hemorrhage, hemosiderin deposition, and lymphocyte depletion in the pancreaticoduodenal lymph node (Doi et al. 1991), an effect which may be secondary to induced hepatic damage. 

Immunological Effects. The effects of carbon tetrachloride on the immune system have not been evaluated in humans. Immune responses were not affected in rats orally exposed to carbon tetrachloride (Smialowicz et al. 1991). Parenteral exposure of animals to carbon tetrachloride has been reported to impair the immune system (Kaminski et al. 1989 Muro et al. 1990 Tajima et al. 1985), and oral exposure caused depletion of lymphocytes, hemorrhage, and hemosiderin deposition in the pancreaticoduodenal lymph node (Doi et al. 1991). These findings are supported by in vitro studies in which the IgM antibody formation response of isolated mouse splenocytes to sheep erythrocytes was inhibited in a dose-dependent manner when the splenocytes were exposed to carbon tetrachloride for 1-3 hours in the presence of cocultured hepatocytes (Kaminski and Stevens 1992). No effects were observed in the absence of cocultured hepatocytes. Mice appear to be more sensitive than rats to carbon tetrachloride-induced immunosuppression, but the biological significance to humans of these reported effects are yet ascertainable from the available data. 

Hemosiderin An iron-containing hematogenous pigment, present in so-called siderophages... 

Pharmacokinetics Readily absorbed after IM administration. Most absorption occurs within 72 hr remainder within 3-4 wk. Bound to protein to form hemosiderin, ferritin, or transferrin. No physiologic system of elimination. Small amounts lost daily in shedding of skin, hair, and nails and in feces, urine, and perspiration. Half-life 5-20 hr. 

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