Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The diabetic foot is prone to foot ulceration, which may lead to ischemia, infection, and the need for amputation. To try to reduce foot ulcer-related hospitalizations and decrease the amputation rate, health care providers need to understand the pathophysiology of the diabetic ulcer, treat ulcers promptly and aggressively, provide revascularization when necessary, prescribe therapeutic shoes, use a team approach, and conduct an intensive, ongoing patient-education program in foot care.
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PMID:Diabetic foot wounds: pathogenesis and management. 920 8

We evaluated the healing potential of human fetal aorta-derived CD133(+) progenitor cells and their conditioned medium (CD133(+) CCM) in a new model of ischemic diabetic ulcer. Streptozotocin-induced diabetic mice underwent bilateral limb ischemia and wounding. One wound was covered with collagen containing 2x10(4) CD133(+) or CD133(-) cells or vehicle. The contralateral wound, covered with only collagen, served as control. Fetal CD133(+) cells expressed high levels of wingless (Wnt) genes, which were downregulated following differentiation into CD133(-) cells along with upregulation of Wnt antagonists secreted frizzled-related protein (sFRP)-1, -3, and -4. CD133(+) cells accelerated wound closure as compared with CD133(-) or vehicle and promoted angiogenesis through stimulation of endothelial cell proliferation, migration, and survival by paracrine effects. CD133(+) cells secreted high levels of vascular endothelial growth factor (VEGF)-A and interleukin (IL)-8. Consistently, CD133(+) CCM accelerated wound closure and reparative angiogenesis, with this action abrogated by co-administering the Wnt antagonist sFRP-1 or neutralizing antibodies against VEGF-A or IL-8. In vitro, these effects were recapitulated following exposure of high-glucose-primed human umbilical vein endothelial cells to CD133(+) CCM, resulting in stimulation of migration, angiogenesis-like network formation and induction of Wnt expression. The promigratory and proangiogenic effect of CD133(+) CCM was blunted by sFRP-1, as well as antibodies against VEGF-A or IL-8. CD133(+) cells stimulate wound healing by paracrine mechanisms that activate Wnt signaling pathway in recipients. These preclinical findings open new perspectives for the cure of diabetic ulcers.
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PMID:Human CD133+ progenitor cells promote the healing of diabetic ischemic ulcers by paracrine stimulation of angiogenesis and activation of Wnt signaling. 1960 84

Diabetic foot ulcers are a major health care problem. Complications of foot ulcers are a leading cause of hospitalization and amputation in diabetic patients. Diabetic ulcers result from neuropathy or ischemia. Neuropathy is characterized by loss of protective sensation and biomechanical abnormalities. Lack of protective sensation allows ulceration in areas of high pressure. Autonomic neuropathy causes dryness of the skin by decreased sweating and therefore vulnerability of the skin to break down. Ischemia is caused by peripheral arterial disease, not by microangiopathy. Poor arterial inflow decreases blood supply to ulcer area and is associated with reduced oxygenation, nutrition and ulcer healing. Necrotic tissue is laden with bacteria apt to grow in such an environment, which also impairs general defence mechanisms against infection. Infections often complicate existing ulcers, but are seldom the cause for ulcers. Protective footwear helps to reduce ulceration in diabetic feet at risk. Relieving pressure on the ulcer area is necessary to allow healing. Blood supply needs to be improved by revascularisation whenever compromised. Systemic antibiotics are helpful in treating acute foot infections, but not uninfected ulcers. Osteomyelitis may underlie a diabetic ulcer and is often treated by resection of the infected bone and always by antibiotics, the mode and length of treatment depending on the adequacy of the debridement. The aim of ulcer bed preparation is to convert the molecular and cellular environment of the chronic ulcer to that of an acute healing wound by debridement, irrigating and cleaning. Moist dressings maintain wound environment favorable for healing. All attempts should be done to prevent diabetic foot ulceration and treat existing ulcers by multidisciplinary teams in order to decrease amputations. Indeed, improvement in ulcer healing has been observed with primary healing rates of 65-85% in mixed series. Even when healed, diabetic foot should be regarded as a life-long condition and treated accordingly to prevent recurrence. Long-term efforts have reduced amputation 37-75% in different European countries over 10-15 years.
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PMID:Treatment of diabetic foot ulcers. 1954 89

Preventing amputations in persons with lower extremity complications of diabetes is a complex endeavor, particularly in those with concomitant ischemia and tissue loss. Fluorescence angiography (Novadaq SPY system) may provide a tool for objective evaluations of tissue viability in the diabetic foot, which is an important indicator of the ability of the diabetic ulcer to heal adequately. The SPY system uses a low-power laser coupled with a charge-coupled device camera and indocyanine green (ICG) to sequence perfusion at the surface of the skin. We present an illustrated example of the potential utility of ICG fluorescence angiography (ICGFA) before and after vascular intervention in a high-risk limb. ICGFA appeared to reveal demarcation between viable and nonviable tissue and real-time perfusion, specifically capillary fill. ICGFA clarified the extent of necessary debridement and provided an immediate indication of improvement in regional perfusion status following revascularization. Future studies involving ICGFA may include pre- and postdebridement and closure perfusion, comparison of tissue perfusion pre- and post-endovascular therapy, and lower extremity flap viability. Future works will also address the consistency of results with ICGFA by analyzing a larger cohort of patients being treated by our unit.
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PMID:Intraoperative fluorescence vascular angiography: during tibial bypass. 2240 40

Half of diabetic ulcers are ischaemic, almost all neuropathic and the problem is often worsened by infection. Ischaemia can often be repaired if diagnosed and treated early enough. At present, ischaemia is often diagnosed far too late. International recommendations emphasize an immediate need for a paradigm change. Ischaemia should always be suspected as a cause of diabetic ulcer unless proven otherwise. Every diabetic patient with a foot ulcer should undergo an immediate clinical and noninvasive vascular assessment. Early diagnosis and undelayed treatment with vascular consultation and necessary revascularizations are prerequisites for successful treatment as "time is tissue".
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PMID:[Assessment of ischaemia of ulcerated diabetic foot and its treatment according to recent international guidelines]. 2501 67

Objective: Neutrophil extracellular traps (NETs) are associated with impaired wound healing in diabetes. This study evaluates the association between NET-specific markers and wound healing among diabetic foot ulcer (DFU) patients treated in a multidisciplinary setting. Approach: Clinical data of diabetic patients with active foot ulcers who presented to our team between January 1, 2016 and June 30, 2017 were recorded. The diabetic ulcer severity score (DUSS) and wound, ischemia, and foot infection (WIfI) score were calculated. NET-specific markers in plasma and wound tissues were tested. The capacity for plasma and platelets to prime neutrophils to release NETs was assessed. The prognostic value of NET-specific markers for wound healing was evaluated. Results: NET-specific markers were significantly higher in DFU patients than in diabetic patients without DFU or healthy controls and were found to correlate positively with DUSS or WIfI score. Elastase levels in ulcer tissue significantly increased in wounds with infections and delayed healing. Higher levels of NET release were observed after the stimulation of plasma or platelets from ulcer-related vessels than from nonulcer-related vessels of the DFU patients. Citrullinated histone 3 (citH3) was identified as a risk factor for wound healing impairment and amputation. The patients with the highest quartile of citH3 levels presented significantly lower healing rates and higher amputation rates than those with the lower three quartiles. Innovation: This study extended current knowledge of NETs on wound healing in DFU patients. Conclusion: NET-specific markers negatively correlated with wound healing in DFU patients, and citH3 is a potential marker.
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PMID:Neutrophil Extracellular Traps Are Markers of Wound Healing Impairment in Patients with Diabetic Foot Ulcers Treated in a Multidisciplinary Setting. 3187 27