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

Chronic venous disease (CVD), mainly due to venous reflux or, sometimes, to venous outflow obstruction, produces a microcirculatory overload leading to the impairment of venous drainage. Venous drainage depends primarily on a major hemodynamic parameter called trans-mural pressure (TMP). TMP is increased in patients affected by CVD, leading to impaired tissue drainage, and, consequently, facilitating the beginning of the inflammatory cascade. Increased TMP determines red blood cell extravasation and either dermal hemosiderin deposits or iron laden-phagocytes. Iron deposits are readily visible in the legs of all patients affected by severe CVD. Local iron overload could generate free radicals or activate a proteolytic hyperactivity of metalloproteinases (MMPs) and/or downregulate tissue inhibitors of MMPs. These negative effects are particularly evident in carriers of the common HFE gene's mutations C282Y and H63D, because intracellular iron deposits of mutated macrophages have less stability than those of the wild type, inducing a significant oxidative stress. It has been demonstrated that such genetic variants increase the risk of ulcers and advance the age of ulcer onset, respectively. The iron-dependent vision of inflammation in CVD paves the way to new therapeutic strategies including the deliberate induction of iron deficiency as a treatment modality for non-healing and/or recurrent venous leg ulcers. The inflammatory cascade in CVD shares several aspects with that activated in the course of multiple sclerosis, an inflammatory and neurodegenerative disease of unknown origin in which the impairment of cerebral venous outflow mechanisms has been recently demonstrated.
 ...
PMID:Inflammation in venous disease. 1897 97

In this review article we discuss current knowledge about iron in the skin and the cutaneous wound healing process. Iron plays a key role in both oxidative stress and photo-induced skin damage. The main causes of oxidative stress in the skin include reactive oxygen species (ROS) generated in the skin by ultraviolet (UVA) 320-400 nm portion of the UVA spectrum and biologically available iron. We also discuss the relationships between iron deficiency, anemia and cutaneous wound healing. Studies looking at this fall into two distinct groups. Early studies investigated the effect of anemia on wound healing using a variety of experimental methodology to establish anemia or iron deficiency and focused on wound-strength rather than effect on macroscopic healing or re-epithelialization. More recent animal studies have investigated novel treatments aimed at correcting the effects of systemic iron deficiency and localized iron overload. Iron overload is associated with local cutaneous iron deposition, which has numerous deleterious effects in chronic venous disease and hereditary hemochromatosis. Iron plays a key role in chronic ulceration and conditions such as rheumatoid arthritis (RA) and Lupus Erythematosus are associated with both anemia of chronic disease and dysregulation of local cutaneous iron hemostasis. Iron is a potential therapeutic target in the skin by application of topical iron chelators and novel pharmacological agents, and in delayed cutaneous wound healing by treatment of iron deficiency or underlying systemic inflammation.
...
PMID:The role of iron in the skin and cutaneous wound healing. 2507 75

The factors preventing healing in venous leg ulcers are still not fully understood. Iron-mediated tissue damage has been hypothesised, yet anecdotally anaemia is also thought to have a negative effect on wound healing. This article summarises the current evidence for these theories and their likely effects in the context of venous ulceration. A comprehensive search of the literature was conducted. Studies suggest that a number of forms of iron including haemosiderin and ferritin are implicated in progression of venous disease, ulcer formation, and impaired healing, which is thought to be primarily free radical mediated. There is a paucity of evidence for the role of iron deficiency and anaemia on ulcer healing; however, there is likely to be a highly complex interplay between the damaging effects of iron on local tissues and the negative effects of anaemia-mediated tissue hypoxia. Studies looking at options to increase local oxygen delivery such as topical haemoglobin suggest that this may have an impact on some aspects of healing, but findings are generally inconclusive. There is growing evidence that locally elevated iron levels may have a detrimental effect on ulcer healing and formation; however, more robust research is needed.
 ...
PMID:An overview of the relationship between anaemia, iron, and venous leg ulcers. 3141 20