Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coronary angioplasty is used to treat coronary disease in many patients. Indications for angioplasty have expanded since it was first performed, mainly as a result of improvement in equipment and techniques. One problem with coronary angioplasty is the phenomenon of renarrowing of the treated coronary lesion, a process called restenosis. The events that constitute restenosis appear to be a universal response to the arterial wall injury of angioplasty. They are currently characterized as follows: platelet adhesion and aggregation on the damaged endothelium and within deep splits into the tunica media; release of platelet-derived growth factors; inflammation of the mechanically injured medial zone; transformation of smooth muscle cells of the tunica media after their activation by several of the growth-promoting substances; migration and proliferation of transformed smooth muscle cells, with secretion of copious amounts of extracellular matrix material; and, finally, termination of the growth process with regrowth of endothelium over the injured area. A decade of research work has helped identify clinical correlates of restenosis after coronary angioplasty procedures. This work is hindered by lack of a uniform angiographic definition of restenosis. In addition, much of the information has come from small studies, with incomplete follow-up and retrospective orientation. Nevertheless, some data are available. Patient-related correlates include male gender, unstable angina, diabetes, and continued smoking after angioplasty. Lesion-related correlates include multilesional and multivessel procedures, higher postangioplasty residual stenosis, proximal vessel location, location in the left anterior descending artery, location in a vein graft, long lesions, and total occlusions. The only consistent procedure-related correlate has been incorrect sizing of the angioplasty balloon to the treated artery. For the purposes of individual patient care, clinical correlates are not helpful. No group of variables has been found to be associated with complete freedom from restenosis, and no group is completely predictive of restenosis. All patients undergoing angioplasty procedures require some follow-up through subsequent months and years. Symptom status and the results of noninvasive studies have been investigated for purposes of follow-up. Symptoms are virtually useless by themselves for predicting restenosis or its absence. When symptom status is combined with exercise thallium 201 scintigraphy performed 4 to 6 months after an angioplasty procedure, the two factors are less than ideal but have a negative predictive value of more than 90%. This means that more than 90% of patients who have neither symptoms nor evidence of ischemia by thallium 201 scintigraphy will not have angiographic restenosis.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Restenosis after coronary angioplasty. 835 9

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a potent enhancer of microvascular permeability and a selective endothelial cell growth factor. In normal human kidney, VPF/VEGF mRNA and protein are strongly expressed by visceral glomerular epithelial cells, and VPF/VEGF may be an important regulator of glomerular endothelial cell function. This study examined 47 renal biopsies from patients with a variety of glomerular diseases for expression of VPF/VEGF mRNA and protein by in situ hybridization and immunohisto-chemistry. In many glomerular diseases, VPF/VEGF-expressing cells were decreased in number or absent in areas of focal or global glomerular sclerosis. Decreased numbers of VPF/VEGF-expressing cells in glomeruli were also noted in amyloidosis, diabetes, crescentic glomerulonephritis, and diffuse endocapillary proliferative glomerulonephritis associated with systemic lupus erythematosus. Normally, release of VPF/ VEGF must be under strict control because it is some 50,000 times more potent than histamine as an inducer of microvascular permeability. Damage to visceral epithelial cells in a variety of glomerular diseases has the potential for releasing relatively large amounts of VPF/VEGF locally, leading to increased glomerular permeability. In addition, because VPF/ VEGF is also an endothelial growth factor, the loss of normal, controlled secretion of VPF/VEGF after damage to visceral epithelial cells could lead to important alterations in glomerular endothelial cell function.
 ...
PMID:Expression of vascular permeability factor (VPF/VEGF) is altered in many glomerular diseases. 873 99

To study platelet-derived microparticle generation in diabetes mellitus, we injected alloxan into male Japanese white rabbits. Injection of alloxan induced diabetes, but did not cause any significant change in various biochemical and hematological parameters. However, diabetic rabbits showed a significant elevation of platelet-derived microparticles from 8 weeks after alloxan injection (week 0: 0.45 +/- 0.24%; week 8: 1.12 +/- 0.61%, p < 0.005). These microparticles are known to have prothrombinase activity, suggesting that they may promote vascular complications in diabetes and may be used as a marker of vascular disease.
 ...
PMID:Platelet-derived microparticles in alloxan-induced diabetes in rabbits. 887 35

Basic fibroblast growth factor (bFGF) is a potent endothelial cell growth factor that does not normally circulate in healthy nonpregnant adults. bFGF has been reported in plasma from patients with certain tumors consistent with a postulated role in tumor angiogenesis. In the present study we used an endothelial cell bioassay to test for a bFGF-like substance in plasma and urine from patients with noninsulin-dependent diabetes mellitus. We found increased bFGF immunoreactivity that correlated with bFGF-like endothelial cell growth-promoting activity in plasma from a subset of diabetic patients with persistent microalbuminuria or overt proteinuria. Plasma (bFGF-like) growth-promoting activity was significantly correlated with glycosylated hemoglobin (P < 0.05), but not patient age, race, degree of proteinuria, or systolic blood pressure. In a group of microalbuminuric or proteinuric diabetic subjects well matched according to baseline clinical characteristics, plasma (bFGF-like) growth-promoting activity was significantly decreased (P < 0.0001) in the subgroup of patients who were being treated with an angiotensin-converting enzyme inhibitor simultaneous to blood drawing for plasma growth assay. In patients not treated with an angiotensin-converting enzyme inhibitor, multiple regression analysis showed that retinopathy was the only variable significantly associated with plasma growth-promoting activity. These results imply that plasma bFGF endothelial cell growth-promoting activity is increased and may contribute to pathophysiology in a heterogeneous subset of noninsulin-dependent diabetes mellitus patients with persistent microalbuminuria or overt proteinuria.
 ...
PMID:Increased basic fibroblast growth factor-like substance in plasma from a subset of middle-aged or elderly male diabetic patients with microalbuminuria or proteinuria. 895 57

Preretinal neovascularization and chronic retinal oedema are the two major sight-threatening complications that can occur during diabetic retinopathy. Ocular neovascularization is strongly associated with retinal ischaemia, and growth factors have been implicated in its pathogenesis. The ischaemic retina is assumed to secrete growth factors that stimulate residual vessels to proliferate. Interest has focused on basic fibroblast growth factor (bFGF), insulin-like growth factor-1 (IGF-1), platelet-derived growth factor (PDGF), transforming growth factor beta (TGF beta) and more recently vascular endothelial cell growth factor (VEGF). Histologic studies have demonstrated the presence of growth factor proteins and receptors and/or their mRNA, mainly VEGF, PDGF, and bFGF, in preretinal membranes of patients with proliferative diabetic retinopathy. Elevated intravitreal levels of IGF-1 and VEGF correlating with neovascular activity have been found in some patients. However, a direct causal relationship between ischaemia, growth factors and neovascularization has not been clearly demonstrated despite considerable research work. To date, the growth factor correlating most closely with neovascularization is VEGF. As many growth factors seem to be produced during the neovascular process, their specific inhibition probably will have limited effects. Laser photocoagulation of the retina has proved beneficial for regression of new vessels, probably through destruction of the ischaemic retina producing neovascular growth factors, and is currently the only treatment for proliferative diabetic retinopathy. Inhibition of IGF-1 by somatostatin analogs has produced unsatisfactory results. Other vascular inhibitors are currently being studied.
Diabetes Metab 1997 Apr
PMID:Growth factors and diabetic retinopathy. 913

We measured levels of platelet-derived microparticles (PMP), which have coagulative activity and are produced by platelet activation or physical stimulation, and CD62P/CD63-positive platelets in patients with diabetes mellitus to determine their clinical significance and effects on complications of diabetes including diabetic nephropathy. We also compared these levels before and after administration of the antiplatelet drug cilostazol. Plasma PMP and CD62P/CD63-positive platelet levels were significantly higher in patients with diabetes mellitus than normal controls. CD62P-positive platelet levels were significantly higher in patients with nephropathy than in patients without complications. After administration of cilostazol, PMP and CD62P/CD63-positive platelet levels were significantly decreased. The increases in platelet activity and its related procoagulant activity appear to account in part for the hypercoagulability observed in diabetes mellitus. Our findings suggest that activated platelets might play a role in the development of diabetic nephropathy. Furthermore, antiplatelet therapy with cilostazol for diabetic patients may be useful as antithrombin therapy including antiplatelet therapy, since it suppresses the production of intrinsic coagulants produced by platelet activation.
 ...
PMID:Significance of platelet-derived microparticles and activated platelets in diabetic nephropathy. 1005 80

The leading cause of amputation in patients with diabetes is the nonhealing foot wound and its complications. The effects of peripheral neuropathy, peripheral vascular disease, and infection often combine to facilitate ulcer development that can lead to gangrene and amputation. In many instances, foot ulcers and amputation can be prevented. The literature over the past 5 years has included information on the infrared thermometry in the diagnosis of infection and acute Charcot change. Pressure downloading has been facilitated by computerized foot scanning systems and the use of prefabricated pneumatic walkers as an alternative to the contact cast. Local wound care is enforced by repeated sharp debridement. Nonhealing ulcers can benefit from biologicals: platelet-derived growth factors and a human dermal replacement containing viable fibroblasts. The most successful outcomes are achieved when interdisciplinary teams are formed to provide coordinated care. The goal of this article is to provide healthcare professionals with an overview of the risks of neuropathic foot injury and to offer strategies for prevention, protection, and reduction of recurrences of the diabetic foot ulcer.
 ...
PMID:The diabetic neuropathic ulcer: an overview. 1008 72

Whole blood flow cytometry is a powerful new laboratory technique for assessment of platelet activation and function. Flow cytometry can be used to measure platelet hyperreactivity, circulating activated platelets, leukocyte-platelet aggregates, and procoagulant platelet-derived microparticles in a number of clinical settings, including acute coronary syndromes, angioplasty, cardiopulmonary bypass, acute cerebrovascular ischemia, peripheral vascular disease, diabetes mellitus, preeclampsia, and Alzheimer's disease. Clinical applications of whole blood flow cytometric assays of platelet function in these diseases may include identification of patients who would benefit from additional antiplatelet therapy and prediction of ischemic events. Circulating monocyte-platelet aggregates appear to be a more sensitive marker of in vivo platelet activation than circulating P-selectin-positive platelets. Flow cytometry can also be used in the following clinical settings: monitoring of glycoprotein IIb-IIIa antagonist therapy, diagnosis of inherited deficiencies of platelet surface glycoproteins, diagnosis of storage pool disease, diagnosis of heparin-induced thrombocytopenia, and measurement of the rate of thrombopoiesis.
 ...
PMID:Laboratory markers of platelet activation and their clinical significance. 1046 51

There is a microcirculation system within the islets of Langerhans. However, little is known about the phenotypic and functional characterization of islet microvascular endothelial cells (MVEC). In this study, we purified MVEC from human pancreatic islets by using Ulex europaeus (Sigma, St. Louis, MO) agglutinin-1 (UEA-1)-coated dynabeads (Dynal A.S., Oslo, Norway). These purified human islet MVEC (HI-MVEC) express von Willebrand factor, take up high levels of acetylated LDL, and upregulate endothelial cell leukocyte adhesion molecule 1 in response to tumor necrosis factor-alpha. Ultrastructure examination shows the presence of microvilli and fenestrations on the cell surface, Weibel-Palade bodies in the cytoplasm, and tight junctions between cells. Furthermore, we show that vascular endothelial cell growth factor contributes to the formation of surface fenestrations on cultured HI-MVEC. After purification, HI-MVEC exhibit a very low proliferation capacity and are strongly resistant to trypsin, compared with other original MVEC. We also demonstrate that alpha-1 proteinase inhibitor (Api) is expressed on HI-MVEC and specifically located at the area of cell-cell junctions. By reverse transcription-polymerase chain reaction, a significant messenger RNA band of Api was found only in HI-MVEC, but not in other organ-derived MVEC, indicating that expression of Api is islet MVEC specific. Antibodies to Api significantly reversed the resistance to trypsin and promoted proliferation of HI-MVEC, suggesting that these specific functional characteristics of HI-MVEC are related to the expression of Api. These results indicate that HI-MVEC exhibit some specific morphological and functional characteristics that differ from MVEC derived from other organs.
Diabetes 1999 Sep
PMID:Expression of alpha-1 proteinase inhibitor in human islet microvascular endothelial cells. 1048 Jun 7

Excessive oxidative stress due to hyperglycemia and glycoxidation leads to an increased production of F2-isoprostanes, one of which, 8-iso-PGF2 alpha, reaches high concentrations in plasma and urine in both insulin-dependent and non-insulin-dependent diabetics. This is associated with an increase in platelet activation, reflected by an increased urinary excretion of platelet-derived TxB2. Improved metabolic control or vitamin E supplementation reduces urinary 8-iso-PGF2 alpha and TxB2, whereas aspirin or indobufen reduces TxB2 but not 8-iso-PGF2 alpha. Since TxB2 in the urine seems to represent the common link between diabetes (as well as other risk factors) and the thrombotic complications of vascular disease, platelet activation due to lipid-glycoxidation is an important aspect in the pathogenesis of vascular complications of diabetes mellitus. Among the various plasma coagulation and fibrinolysis factors that are found to be altered in diabetes, the increased level of plasminogen activator inhibitor (PAI-1) in the plasma and in the vessel wall is of the utmost importance. Indeed, it is suspected that the atherosclerotic plaques formed in the presence of high concentrations of PAI-1 are more prone to rupture and ensuing thrombosis. The thrombosis-oriented modifications of blood platelets, coagulation and fibrinolysis are an important cause behind the high prevalence of vascular events in diabetes.
 ...
PMID:[Diabetes, coagulation and vascular events]. 1074 54


<< Previous 1 2 3 4 5 6 7 Next >>