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

Intravitreal triamcinolone acetonide (IVTA) has been applied in exponentially increasing frequency for various intraocular neovascular and edematous diseases, including diabetic macular edema, proliferating diabetic retinopathy, neovascular glaucoma due to proliferative diabetic retinopathy, and chronic prephthisical ocular hypotony as complication of the surgical treatment of diabetic retinopathy. In diabetic macular edema, the edema may almost completely resolve, and visual acuity may increase as much as macular ischemia and the tissue destruction by the diabetic process may allow. For proliferative diabetic retinopathy and neovascular glaucoma, investigations have suggested an antiangiogenic effect of IVTA. Using a side effect of IVTA, i.e. steroid-induced elevation of intraocular pressure, IVTA may be applied for the therapy of chronic prephthisical ocular hypotony due to an insufficiency of the ciliary body as consequence of a surgical treatment of proliferative diabetic retinopathy. The complications of IVTA include secondary ocular hypertension in about 40% of the eyes, medically uncontrollable high intraocular pressure leading to antiglaucomatous surgery in about 1-2%, posterior subcapsular cataract and nuclear cataract leading to cataract surgery in about 15-20%, especially in elderly patients within 1 year after injection, postoperative infectious endophthalmitis with a rate of about 1:500 or 1:1,000, noninfectious endophthalmitis, and pseudo-endophthalmitis. IVTA can be combined with other intraocular surgeries including cataract surgery, particularly in eyes with iris neovascularization due to diabetic retinopathy. Cataract surgery performed some months after the injection does not show a markedly elevated rate of complications. If vision increases and eventually decreases after an IVTA injection, the injection can be repeated. The duration of the effect of a single IVTA is dosage dependent (about 6-9 months with 20 mg, and about 2-4 months with 4 mg).
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PMID:Intravitreal triamcinolone acetonide for diabetic retinopathy. 1724 81

Indocyanine green (ICG) is nearly exclusively eliminated from the blood by the liver and the ICG plasma disappearance rate (ICG-PDR) enables assessment of liver blood flow and function. The ICG-PDR which nowadays can be measured non-invasively by a transcutaneous system enables bedside and "on-line" regional monitoring in critically ill patients. So far, only complete lack of ICG-PDR as a sign of non-existing perfusion during liver transplantation has been reported. We describe two patients who developed mesenteric ischemia accompanied by an inadequate increase after revascularisation and an acute drop in the ICG-PDR. In both cases, a computed tomography scan was performed and confirmed an acute abdominal ischemia as indicated by ICG-PDR. Both patients suffered from occlusion of the truncus coeliacus while hepato-splanchnic perfusion via the A. mesenterica superior and the V. portae was maintained. ICG-PDR may be helpful for early detection of hepato-splanchnic ischemia and enables rapid and sufficient initiation of diagnostic and therapeutic procedures. In conclusion, ICG-PDR may be regarded as a clinically attractive bedside monitoring tool for early and reliable detection of partial ischemia in the hepato-splanchnic tract.
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PMID:[Indocyanine green plasma disappearance rate. Marker of partial hepato-splanchnic ischemia]. 1727 43

Ocular vascular diseases such as diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration, whose population increases along with aging, have become leading causes of severe visual disturbance. Macular edema and serous retinal detachment are associated with abnormal vascular leakage and tractional retinal detachment, and neovascular glaucoma is caused by retinal neovascularization. Such ocular vascular diseases are caused by vascular cell aging and vascular damage associated with lifestyle-related diseases including diabetes mellitus, hypertension, hyperlipidemia, and obesity. In the present study, we investigated molecular mechanisms in such vascular deficiencies using vascular cell biology methodology, and we propose novel strategies for the treatment of such vascular diseases. Along with aging, oxidative stress and physical stress, such as mechanical stretch, continuously and directly insult vascular cells. Such stress induces apoptosis by intracellular signaling through stress kinases in cultured retinal vascular cells. Inhibition of such stress kinases could be an effective treatment to protect the vascular cells against age-related damage. In a retinal vascular developmental model, pericyte loss causes pathology mimicking macular edema and proliferative diabetic retinopathy. Angiopoietin 1 (Ang 1) secreted by pericytes suppresses oxidative stress-induced intracellular signaling through stress kinases linked to cell apoptosis and normalizes such retinal pathology. This suggests that the paracrine action of Ang 1 in the pericytes is necessary to sustain normal retinal vasculature, and that Ang 1-triggered intracellular signaling is useful for the treatment of vascular cell pathology associated with pericyte loss. In diabetic retinopathy and retinal vein occlusion, retinal vessels regress along with retinal vascular cell apoptosis, and the retina becomes ischemic followed by pathological retinal neovascularization. VEGF has been recognized as a predominant factor to induce the ischemic retinal neovascularization. We found that retinal vascular cells have a characteristic pattern in VEGF receptor expression, which causes vascular pathology more frequently in the retina than in other organs. Neuropilin 1 (NRP 1), which enhances VEGF receptor function, is abundantly expressed in the retinal endothelial cells and is upregulated by VEGF itself and by hypoxia to regulate a positive feedback mechanism in retinal neovascularization. This receptor could be a unique target for retina-specific therapy. Lifestyle-related diseases increase along with aging and have further increased due to changes in Japanese lifestyle imitating that of Western countries. We found that the renin-angiotensin system which regulates hypertension and cardiovascular diseases, and adipocytokines which are abnormally secreted in obesity, act as proangiogenic factors. Regulation of such lifestyle-related disease factors is important for the treatment of retinal vascular diseases. Finally, we found that erythropoietin is an ischemia-induced angiogenic factor that acts independently and as potently as VEGF in proliferative diabetic retinopathy (PDR). Our study utilizing human vitreous samples demonstrates that the VEGF level is particularly high and strongly associated with angiogenic activity in PDR patients. The potential of VEGF inhibitors has recently been recognized in clinical applications. The manipulation of each angiogenic factor and adipocytokine that we report here could become potential therapy in the near future.
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PMID:[Aging and retinal vascular diseases]. 1740 63

Diabetic retinopathy is a leading cause of visual disturbance in adults. In proliferative diabetic retinopathy, ischemia-induced pathologic growth of new blood vessels often causes catastrophic loss of vision. Besides VEGF, the existence of another potent ischemia-induced angiogenic factor is postulated. Since ischemia-inducible erythropoietin (Epo) has recently been identified its angiogenic properties, we investigated its potential role during retinal angiogenesis in proliferative diabetic retinopathy (PDR). The vitreous Epo level in patients with PDR was significantly higher than that in nondiabetic patients. Multivariate logistic regression analyses indicated that Epo and VEGF were independently associated with PDR and that Epo was more strongly associated with PDR than VEGF. Blockade of Epo inhibits retinal neovascularization in vivo, and inhibits endothelial cell proliferation response to PDR vitreous in vitro. Our data provide strong evidence that erythropoietin is a potent retinal angiogenic factor independent of VEGF and is capable of stimulating ischemia-induced retinal angiogenesis in proliferative diabetic retinopathy. Inhibition of such molecular mechanisms in the retinal angiogenesis could be a new therapeutical strategy in halting or preventing pathologic angiogenesis in diabetic retinopathy.
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PMID:Novel role of erythropoietin in proliferative diabetic retinopathy. 1748 72

Diabetic retinopathy is one of the most common diabetic complications, and is a major cause of new blindness in the working-age population of developed countries. Progression of vascular abnormalities, including the selective loss of pericytes, formation of acellular capillaries, thickening of the basement membrane, and increased vascular permeability characterizes early nonproliferative diabetic retinopathy (NPDR). Capillary occlusion, as shown on fluorescein angiograms, is also one of the earliest clinically recognizable lesion of NPDR. In response to capillary non-perfusion, there is dilation of neighbouring capillaries, leading to early blood-retinal barrier breakdown, capillary non-perfusion, and endothelial cell injury and death. The resulting ischemia leads to increased production of growth factors, and the development of proliferative diabetic retinopathy (PDR), which is characterized by growth of new vessels and potential severe and irreversible visual loss. The exact pathogenic mechanism by which capillary non-perfusion occurs is still unclear but growing evidence now suggests that increased leukocyte-endothelial cell adhesion and entrapment (retinal leukostasis) in retinal capillaries is an early event associated with areas of vascular non-perfusion and the development of diabetic retinopathy. The leukocytes in diabetic patients are less deformable more activated, and demonstrate increased adhesion to the vascular endothelium. This review summarizes the current literature on the role of leukocytes in the pathogenesis of capillary occlusion, and discusses the potential of leukostasis as a new promising target in the treatment of diabetic retinopathy.
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PMID:Leukocytes in diabetic retinopathy. 1822 Jun 51

Diabetes mellitus (DM) can cause many systemic complications, including proliferative diabetic retinopathy (PDR). Retinal neovascularization (RNV) is the typical symptom of PDR, representing an important risk factor for severe vision loss in patients with DM. Diabetic hyperglycemia plays a major role in the destruction of retinal capillary walls, resulting in retinal ischemia and up-regulation of vascular endothelial growth factor (VEGF), leading to neovascularization. The transcriptional regulation of VEGF is mediated by transcription factor hypoxia-inducible factor 1 (HIF-1). Insulin is the mainstay of treatment for DM, but some studies have demonstrated that insulin had the ability to stimulate VEGF and HIF-1 expression in retinal pigment epithelial cells, retinal epithelial cells and vascular smooth muscle cells. In addition to the mitogenic effect of insulin makes it as an assistant agent has long been used in vitro cell culture. Other studies confirmed that insulin increased leukostasis in retinal microcirculation. Based on these experimental results, we hypothesize that long-term insulin therapy maybe improves the expression of VEGF and increase the risk of RNV, eventually deteriorates PDR in patients with DM.
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PMID:Insulin may cause deterioration of proliferative diabetic retinopathy. 1902 44

Diabetic retinopathy (DR) remains the major threat to sight in the working age population. Diabetic macular edema (DME) is a manifestation of DR that produces loss of central vision. Macular edema within 1 disk diameter of the fovea is present in 9% of the diabetic population. Proliferative diabetic retinopathy (PDR) is a major cause of visual loss in diabetic patients. In PDR, the growth of new vessels from the retina or optic nerve, is thought to occur as a result of vascular endothelial growth factor (VEGF) release into the vitreous cavity as a response to ischemia. Furthermore, VEGF increases vessel permeability leading to deposition of proteins in the interstitium that facilitate the process of angiogenesis and macular edema. This review demonstrates multiple benefits of intravitreal bevacizumab on DR including DME and PDR. The results indicate that intravitreal bevacizumab injections may have a beneficial effect on macular thickness and visual acuity (VA), independent of the type of macular edema that is present. Therefore, in the future this new treatment modality could replace or complement focal/grid laser photocoagulation in DME. In addition, in PDR, this new option could be an adjuvant agent to PRP so that more selective therapy may be applied.
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PMID:Intravitreal bevacizumab for diabetic retinopathy. 1919 97

A 58-year-old woman with non-proliferative diabetic retinopathy presented with decreased visual acuity from chronic macular edema. She had undergone multiple treatments previously, including focal laser treatment and intravitreal triamcinolone acetonide. Within 2 days of treatment with intravitreal bevacizumab, the patient noted a significant decrease in visual acuity. Fluorescein angiogram demonstrated an enlargement of the foveal avascular zone and persistent late leakage following intravitreal bevacizumab; optical coherence tomography performed before and after treatment revealed persistent cystoid macular edema. The use of intravitreal bevacizumab in chronic, refractory diabetic macular edema may cause acute visual acuity loss by disrupting an already fragile vascular perfusion status, leading to macular ischemia.
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PMID:Acute visual acuity loss following intravitreal bevacizumab for diabetic macular edema. 1920 2

Diabetic retinopathy is the leading cause of vision loss among working-age people in the United States. The hallmark of diabetic retinopathy is vascular compromise. Increased vascular permeability leads to the development of diabetic macular edema, which is the major cause of vision loss in patients with diabetic retinopathy. Vascular occlusion causes retinal ischemia and subsequent angiogenesis (proliferative diabetic retinopathy), which increases the risk for vitreous hemorrhage and retinal detachment. Over the past 30 years our understanding of the pathophysiology of diabetic retinopathy has evolved greatly and has fostered the development of many novel treatments for this condition. This article will review promising new local and systemic pharmacologic treatments for diabetic macular edema and proliferative diabetic retinopathy.
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PMID:Novel Pharmacologic Approaches for the Management of Diabetic Retinopathy. 2035 67

Proliferative diabetic retinopathy is a consequence of retinal ischemia due to capillary occlusion resulting from damage to the retinal microvascular endothelium. Recent evidence suggests that high levels of bone-marrow derived circulating endothelial progenitor cells (EPCs) contribute to the pathological neovascularization of ischemic tissues and are a critical risk factor for the development of these complications. In the absence of a consensus definition of a circulating EPC and its surface markers in humans we evaluated the functional properties of CD34(+) CD45(-) endothelial colony forming cells (ECFCs) in patients with proliferative diabetic retinopathy (PDR). Higher levels of circulating CD34(+) CD45(-) cells were observed in patients with PDR compared to controls. However, ECFCs from patients with PDR were impaired in their ability to migrate towards SDF-1 and human serum, incorporate into and form vascular tubes with human retinal endothelial cells. The results from these pilot studies suggest that ECFCs from patients with PDR are mobilized into the circulation but may be unable to migrate and repair damaged capillary endothelium. This suggests that ECFCs may be a potential therapeutic target in the prevention and treatment of diabetic vascular complications.
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PMID:Impaired function of circulating CD34(+) CD45(-) cells in patients with proliferative diabetic retinopathy. 2049 38


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