الفهرس 
IRON TRAFFIC AND HOMEOSTASISOnly 14 pages are availabe for public view
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Abstract
Iron is a vital element in both humans and animals; it’s important biological role in many metabolic processes and in critical enzyme reactions is concerned with oxygen and electron transport and the cellular production of energy.
If iron concentrations is high this can be toxic, this lead to iron overload diseases which may be cause organ damage. The synthesis and secretion of the hepatic hormone hepcidin is increased in response to liver iron overload and inflammation and is decreased in response to red cell demand or hypoxia. Most recessive diseases leading to primary iron overload known as HH result from inadequate hepcidin production leading to inappropriate iron accumulation. The mechanisms responsible for disturbed iron homeoeostasis in HH are poorly understood. However, results of some studies indicate a link between serum hepcidin, and intestinal iron absorption, suggesting that this molecule could play a part in hepatic iron overload toxicity.
Hepcidin is a peptide hormone a central negative regulatory role in systemic iron homeostasis through a hormonal action: digestive iron absorption by enterocytes and iron recycling by macrophages. Studies in humans have focused in the crucial role of hepcidin in the regulation of iron homeostasis. Dysregulation of hepcidin production results in a variety of iron disorders.
Hepcidin production is mainly hepatic and to less extent extra-hepatic, its elimination is renal and its expression is the result of the interplay between multiple stimuli including iron, inflammation, and erythropoiesis.
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SUMMARY AND CONCLUSION:
Hepcidin deficiency is the cause of iron overload in HH, iron-loading anemias and hepatitis C. Hepcidin excess is associated with AI, CKD and IRIDA.
Hepatitis C Virus (HCV) infection is the most common cause of chronic hepatitis in HD patients.
HCV infection is an important cause of morbidity and mortality in the dialysis population. The problem is more pronounced after renal transplantation, it seems that immunosuppressive drugs facilitate HCV replication and accelerate hepatic lesions.
HCV infected HD patients need lower rHu-EPO and iron supplementation compared to non infected HD patients.
IV iron administration reverses suboptimal response to rHu-EPO administration in HD patients regardless of HCV serology. There is however subtle increase of transaminases level in HCV positive patients.
Diagnostic and therapeutic applications of hepcidin hormone are beginning to emerge. Accordingly, hepcidin concentrations in different forms of anemia vary widely and may have diagnostic potential in differentiating between the various types of anemia. Furthermore, in cases where hepcidin is a causative factor in anemia, hepcidin-targeted therapies (Hepcidin agonists & Hepcidin antagonists) may improve treatment options for the patients.
Hepcidin agonists would be useful for preventing iron overload in nontransfused β-thalassemias and other iron-loading anemias.
Hepcidin antagonists would be expected to benefit patients with diseases of hepcidin excess. The curical role of hepcidin antagonists such as vitamin C, EPO and mono clonal antibodies will be a beneficial treatment of hypo-responsiveness to ESA therapy in ESRD patients and IRIDA.
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SUMMARY AND CONCLUSION:
We can conclud from our research essay; interestingly that the very important role of hepcidin as a key negative regulatory hormone in iron homeostasis and its clinical role as a future diagnostic biochemical marker in different types of anemias and HH, and as a therapeutic agent in treating more-complex iron metabolic and endocrine disorders, such as beta-thalassaemia, iron-loading anaemias, IRIDA, and anemia of inflammation.
But still hepcidin clinical implications is in need to handling the limitations for its use due to technical difficulties and expensive cost and further wide clinical research works for both a better fully understanding of pathophysiology and for clinical purposes in which hepcidin will help.
The present study of relation of hepcidin and both iron parameters and liver enzyme activity in the regular HD patients with CHC viral infection showed a statistical significance versus the three study groups (HCV +ve ESRD group, HCV -ve ESRD group and control healthy group) concerning serum pro-hepcidin, CRP (US), Hb, all iron parameters (except s.ferritin), liver functions (transaminases) and renal profile (creatinine-BUN-calcium-phosphorus). A non significant correlation between pro-hepcidin and all study parameters (except with TIBC) especially iron parameters and liver profile ; these may due to The opposing multi-factorial aspects implicated in our study ,multi-regulatory stimuli inter-playing with regulation of hepcidin production in our study and also may be due to a little numbers of the subject groups (total No.=40).
The opposing multi-factorial aspects implicated in our study such as chronic inflammatory status as in CHC , inflammatory status of hemodialysis procedure , iron overloading status as in CHC , iron deficiency and anemia of chronic kidney disease , IRIDA status due to hypo-responsiveness to ESA therapy in ESRD patients , defective 122
SUMMARY AND CONCLUSION:
hepcidin synthesis as in cases with chronic liver disease in CHC patients , hepcidin accumulation due to loss of kidney function could decrease hepcidin clearance (Renal excretion is a major route of hepcidin clearance) and lead to development of iron-restrictive anemia and inability of dialyzer membrane to remove excess hepcidin-25 in some HD patients (dialyzer membrane did not affect the pro-hepcidin level).
The factors included in our study increasing hepcidin level were more effective than factors blocking its production ;these may decrease the complications of CHC in HD patients due to lack of hepatic iron deposition; improving the ACD of HD patients with CHC and decrease resistance to ESA therapy.