Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metals such as lead, zinc, copper, aluminum and manganese have been implicated in neuropsychiatric disorders. However, until fairly recently the role of iron in brain function was rather obscure, because little attention was paid to its metabolism in the brain. It is now apparent that maintenance of brain iron homoeostasis is important for the normal functioning of his organ. Most of the studies have been directed towards the cognitive and attentional deficit resulting from nutritional iron deficiency. Evidence so far suggests subsensitivity of striatal dopamine neurotransmission. By contrast the selective increase in free iron in the substantia nigra pars compacta of parkinsonian brains is thought to initiate oxidative stress, from iron-induced liberation of cytotoxic oxygen free radicals. Such radicals are known to promote membrane fluidity, alteration in cellular calcium homoeostasis, lipid peroxidation and finally cell death in systemic organs. Evidence supporting similar processes being responsible for nigrostriatal dopamine neuron degeneration in Parkinson's disease is now becoming available. Such possibilities afford the development of neuroprotective drugs as a means to retard the progression of this disorder. These include other selective monoamine oxidase B inhibitors, iron chelators with the ability to cross the blood-brain barrier, selective calcium channel antagonists and mitochondrial electron transport system protectors.
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PMID:Iron in brain function and dysfunction with emphasis on Parkinson's disease. 164 57

Anemia is one of the most serious complications in patients on dialysis. Erythropoietin improves the anemia. However, erythropoietin resistance is sometimes encountered from causes such as functional iron deficiency, secondary hyperparathyroidism, blood loss, or interaction with other drugs. To clarify the interaction between erythropoietin and the renin-angiotensin system, we studied the maintenance dose of recombinant human erythropoietin (rHuEPO) in patients on continuous ambulatory peritoneal dialysis (CAPD) with and without angiotensin converting enzyme inhibitor (ACEIs), angiotensin II type I receptor blockers (ARBs), and calcium channel blockers. We divided 36 hypertensive patients on CAPD into three groups--an ACEI group (n = 12), an ARB group (n = 12), and a Ca channel blocker group (n = 12)--and then we compared the doses of rHuEPO required to maintain the patients' hematocrit (Hct) above 30%. In the Ca channel blocker group, the weekly dose of erythropoietin had not changed significantly at the end of the study (74 +/- 7 U/kg at the end vs. 76 +/- 8 U/kg at the start). The (oral) ACEI group needed a significantly higher weekly dose of erythropoietin at the end of the study (89 -/+ 9 U/kg at the end vs. 74 -/+ 8 U/kg at the start, p < 0.01). The (oral) ARB group also needed a significantly higher weekly dose of erythropoietin at the end of the study (82 -/+ 10 U/kg at the end vs. 76 +/- 8 U/kg at the start, p < 0.05). Furthermore, the weekly dose of erythropoietin required in the ACEI group was significantly larger than that required in the ARB group. We conclude that treatment with ACEIs and ARBs induces erythropoietin resistance in patients on CAPD. The inhibitory effect of ARBs on erythropoiesis is less than that of ACEIs.
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PMID:Erythropoietin resistance in patients on continuous ambulatory peritoneal dialysis. 1538 8

Several iron-related parameters have been reported to show significant heritability, and thus, seemed to be genetically regulated. A genome wide family-based study revealed two regions that showed a linkage signal with transferrin receptor levels. The aim of the study was to identify genetic markers associated with iron status biomarkers. Ten SNPs selected from the literature were tested, and parameters related to iron metabolism were analysed, in a group (n=284) of Spanish women. Data were analyzed using Bayesian Model Averaging (BMA) test and decision trees. The rs1375515, located in an intronic region of the calcium channel gene CACNA2D3, showed strong associations with levels of mean corpuscular volume according to BMA test, and with levels of haemoglobin and ferritin according to decision trees. The allele G was associated to low levels of these parameters which suggests higher iron deficiency anaemia risk. This SNP along with the C282Y mutation explained significant differences in the distribution of individuals in three iron-related clinical phenotypes (normal, iron deficient and iron deficiency anaemic). In conclusion, the rs1375515, or other genetic polymorphisms in linkage, may play important roles in iron status, probably by affecting the function of a calcium channel. These findings may be useful for further investigation in the etiology of iron diseases.
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PMID:Identification of a novel quantitative trait nucleotype related to iron status in a calcium channel gene. 2332 78

Iron is a key micronutrient for the human body and participates in biological processes, such as oxygen transport, storage, and utilization. Iron homeostasis plays a crucial role in the function of the heart and both iron deficiency and iron overload are harmful to the heart, which is partly mediated by increased oxidative stress. Iron enters the cardiomyocyte through the classic pathway, by binding to the transferrin 1 receptor (TfR1), but also through other routes: T-type calcium channel (TTCC), divalent metal transporter 1 (DMT1), L-type calcium channel (LTCC), Zrt-, Irt-like Proteins (ZIP) 8 and 14. Only one protein, ferroportin (FPN), extrudes iron from cardiomyocytes. Intracellular iron is utilized, stored bound to cytoplasmic ferritin or imported by mitochondria. This cardiomyocyte iron homeostasis is controlled by iron regulatory proteins (IRP). When the cellular iron level is low, expression of IRPs increases and they reduce expression of FPN, inhibiting iron efflux, reduce ferritin expression, inhibiting iron storage and augment expression of TfR1, increasing cellular iron availability. Such cellular iron homeostasis explains why the heart is very susceptible to iron overload: while cardiomyocytes possess redundant iron importing mechanisms, they are equipped with only one iron exporting protein, ferroportin. Furthermore, abnormalities of iron homeostasis have been found in heart failure and coronary artery disease, however, no clear picture is emerging yet in this area. If we better understand iron homeostasis in the cardiomyocyte, we may be able to develop better therapies for a variety of heart diseases to which abnormalities of iron homeostasis may contribute.
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PMID:Iron and the heart: A paradigm shift from systemic to cardiomyocyte abnormalities. 3110 22