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  • 1
    ISSN: 1432-5233
    Keywords: Diabetes mellitus ; Diabetic retinopathy ; Endothelium ; Growth factors ; Pericytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Selective loss of capillary pericytes occurs early and specifically in diabetic retinopathy. We have investigated whether blood derivatives from patients with longterm type 1 (insulin-dependent) diabetes and no retinopathy differ from those with retinopathy and/or non-diabetic controls in their ability to stimulate DNA synthesis in cultured bovine retinal pericytes and endothelial cells. As a general trend, whole blood serum, platelet-rich plasma and platelet-free plasma from patients without and with retinopathy stimulated thymidine incorporation in both cell types less than derivatives from controls. Serum, 0.1% v/v final concentration in culture medium, from patients without retinopathy was less active (114.5±24.5% of a standard stimulus produced by 0.1% fetal calf serum) than that from patients with the complication (132.6±20.8%,P=0.003) and both were less potent than control sera (143.6±28.0%,P〈0.001 andP=0.013, respectively). Lack of support from circulating factor(s) may contribute to the disappearance of pericytes from the capillary wall in diabetes but further investigations are necessary to clarify the mechanisms that prevent the development of microangiopathy in some patients.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-5233
    Keywords: Diabetes mellitus ; Diabetic retinopathy ; Endothelial cells ; Growth factors ; Pericytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pericytes disappear early, selectively and specifically from retinal capillaries in diabetic microangiopathy, but little is known of their growth and turnover in health and disease. We have studied the effects of human blood derivatives and of a panel of individual growth factors on [3H]thymidine incorporation in bovine retinal pericytes and endothelial cells. Human serum and platelet-rich plasma stimulated incorporation of the nucleotide in a dose-dependent manner in both cell types, and did so more potently than platelet-free plasma. Consistent and significant stimulation of DNA synthesis in pericytes was observed with basic fibroblast growth factor (ED50= 1.8×10−13 mol/l), acidic fibroblast growth factor (7.4× 10−12 mol/l), insulin-like growth factor 1 (8.6×10−10 mol/l), insulin (158 μU/ml) and endothelin-1 (6.1×10−10 mol/l). Transforming growth factor β1 inhibited DNA synthesis (ID50=3.6×10−10 mol/l) and so did heparin (1.4×10−6 mol/l) and low molecular weight heparin (2.9×10−6 mol/l). Retinal endothelial cells were stimulated by basic fibroblast growth factor (3.2×10−13 mol/l) and acidic fibroblast growth factor (1.3×10−9 mol/l), and inhibited by transforming growth factor β1, (1.6×10−12 mol/l). Neither cell type was stimulated by platelet-derived growth factor (A+B chain heterodimer), epidermal growth factor, growth hormone, or nerve growth factor (7S complex). The characteristics and active concentrations of the above growth factors suggest that none is solely responsible for the pericyte mitogenic activity of platelets, serum or plasma. Some, though, may play a role in the regulation of pericyte turnover through paracrine mechanisms which should be further investigated.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 18 (1980), S. 217-221 
    ISSN: 1432-0428
    Keywords: Diabetes ; diabetic retinopathy ; platelets ; platelet aggregation ; platelet shape change
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In vitro platelet aggregation has been studied in 29 normal subjects and 35 diabetic patients with retinopathy by conventional aggregating agents and by a new technique which evaluates the platelet shape change. — Platelet shape change, expressed as % light transmission variation induced by the addition of ADP (10 μmol/l) in calcium-deprived platelet rich plasma, was determined. Significant differences were found between the controls (12.6±0.7%) and the 35 diabetics (15.6±1.0%, p 〈0.02) and between controls and the subgroup of patients with proliferative retinopathy (17.3±1.1%, n=15, p〈0.001). Platelet aggregation induced by ADP, collagen and ristocetin did not show significant differences between normal and diabetic subjects. — The shape change is the physiological early phase of platelet aggregation and is related to energy requiring mechanisms. As yet unexplored metabolic abnormalities at this stage could account for previously described platelet abnormalities in diabetes.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 26 (1984), S. 173-179 
    ISSN: 1432-0428
    Keywords: Diabetic maculopathy ; proliferative retinopathy ; photocoagulation ; vitrectomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Diabetic retinopathy, hitherto the most common cause of blindness in those between 30–64 years of age has become treatable. Both diabetic maculopathy and proliferative retinopathy can be treated effectively by photocoagulation. The treatment is most successful if given early, before visual loss becomes irreversible. Recently, vitrectomy with additional microsurgical techniques has been developed and shown to be effective in restoring vision to many patients blind from the complications of proliferative retinopathy.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Diabetic microangiopathy ; platelet aggregation ; platelet adhesiveness ; platelet function ; β-globulins ; blood coagulation factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In 16 diabetic patients with microangiopathy, survival of 111In-labelled autologous platelets, mean platelet volume, megathrombocyte index, spontaneous and ADP-induced platelet aggregation, platelet retention, β-thromboglobulin, von Willebrand factor and factor VIII-related antigen were measured; the splenic uptake of radioactive label was quantitated in six patients. Compared with normal subjects, increased platelet aggregation (p〈0.01), von Willebrand factor (p〈0.02) and factor VIII-related antigen (p〈0.02) were observed. Platelet survival was shortened in two patients. It correlated inversely with the splenic radioactivity uptake (r=-0.95; p〈0.01), suggesting that platelets ended their life in the spleen, not in the microcirculation. No significant relationships were found between the various tests performed, nor between these and the severity of microangiopathy or other clinical data. In spite of the evidence for altered platelet function in patients with diabetic microangiopathy, currently available tests are not specific enough to clarify the nature of these changes or their possible pathogenic significance.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Lipoprotein (a) ; Type 1 (insulin-dependent) diabetes mellitus ; diabetic retinopathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Progressive capillary occlusion often leads to severe retinopathy within 15–20 years of the onset of Type 1 (insulin-dependent) diabetes mellitus. Lipoprotein (a), a complex formed by apolipoprotein (a), apo B-100 and lipids, is considered an independent, genetically determined, predictor of cardiovascular disease. It may have antifibrinolytic properties in view of its similarity to plasminogen. To test the hypothesis that circulating lipoprotein (a) is associated with the process that leads to clinically active diabetic retinopathy, we measured the circulating levels of apolipoprotein (a) (which are strictly correlated with those of lipoprotein (a)) in two groups of patients with Type 1 diabetes of at least 15 years duration: 25 with active retinopathy and 27 without clinically detectable retinal lesions. Thirty-eight healthy subjects of the same age and sex served as controls. Serum apolipoprotein (a) was higher in the patients with active retinopathy (36(2-193) U/dl, geometric mean and range) than in those without clinically detectable retinal lesion (17(1–160)) and the control subjects (14(0–115)), p 〈 0.01 in both cases. The distribution of apolipoprotein (a) levels was skewed to the left, as expected, in the patients without clinically evident retinal lesions and the control groups, but there was a bimodal trend of distribution among those with active retinopathy. The levels of glycated haemoglobin were similar in the two groups of diabetic patients, and no significant differences were found for total and HDL cholesterol, triglycerides or apolipoproteins A1 and B between them and the control subjects. These preliminary results suggest that serum apolipoprotein (a) is elevated in patients with active retinopathy. The role of this lipoprotein as a predictor or a pathogenic effector of diabetic retinopathy, or both deserves further investigation.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Keywords Advanced glycation end products ; diabetic retinopathy ; pericyte ; endothelial cell ; AGE-receptor.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The toxic effects of advanced glycation end products (AGEs) on bovine retinal capillary pericytes (BRP) and endothelial cells (BREC) were studied. AGE-modified bovine serum albumin (AGE-BSA) was toxic to BRP. At a concentration of 500 μg/ml it reduced the BRP number to 48 ± 3 % (p 〈 0.05) of untreated controls, as determined by cell counting with haemocytometer. AGE-BSA was also toxic to bovine aortic endothelial cells (BAEC) reducing cell number to 84 ± 3.1 % of untreated controls. Under similar conditions, low concentrations (62.5 μg/ml) of AGE-BSA were mitogenic to BREC increasing the cell proliferation to 156 ± 11 % (p 〈 0.05) above that of untreated controls. At a higher dose of 500 μg/ml AGE-BSA decreased the proliferation of BREC to 85 ± 6 % of untreated controls. Immunoblot analysis demonstrated that BRP and BREC express the p60 AGE-receptor. Retinal capillary bed from the human also stained positively for the p60 AGE-receptor. Addition of 0.25 μg/ml of p60 AGE-receptor antibody was able to block the effects of AGE-BSA on BRP and BREC. The level of binding of [125I]-labelled AGE-BSA to the cell surface was small but significant among the three cell types. There was also an increase in the internalized pool of radioligand in BRP and BREC but this was very much lower than in BAEC. In all the cell types the internalized pool of [125I]-labelled AGE-BSA was much larger than the amount associated with the cell surface. Degradation products were not detected in the media over the 24-h incubation of the cells with [125I]AGE-BSA. The binding of [125I]-labelled AGE-BSA to the cell surface was prevented by the addition of p60 AGE-receptor. These results suggest that the interaction of AGE-modified proteins with the membrane-bound AGE-receptor may play an important role in the pathogenesis of diabetic retinopathy. [Diabetologia (1997) 40: 156–164]
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 11 (1975), S. 27-33 
    ISSN: 1432-0428
    Keywords: Diabetic retinopathy ; retinal blood flow ; flourescein ; angiography ; mean transit time
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Retinal blood flow was studied in 9 normal volunteers and 36 diabetic patients. The method used was based on the measurement of the mean transit time of flourescein in the superior temporal quandrant of the retina and on estimation of the vascular volume by measuring vessels diameters. The results showed that patients with mild or no retinopathy had significantly increased volume flow compared with normals, those with moderate retinopathy had a slight but not significant increase and those with severe retinopathy had blood flow similar to that found in normals. The mean transit time was reduced significantly in those with mild or no retinopathy, but was similar to normals in those with moderate and severe retinopathy. Following succesful pituitary ablation and photocoagulation retinal blood flow was reduced compared with pre-treatment studies.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Keywords Diabetic retinopathy ; microaneurysms ; UKPDS ; Type II diabetes ; diabetes ; complications.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. To determine whether microaneurysms, in the absence of other lesions, have a predictive role in the progression of diabetic retinopathy in Type II (non-insulin-dependent) diabetes mellitus. Methods. Retinal photographs taken at diagnosis in patients participating in the United Kingdom Prospective Diabetes Study, and thereafter at 3 yearly intervals, were assessed using a modified Early Treatment of Diabetic Retinopathy grading system for lesions of diabetic retinopathy and end points of vitreous haemorrhage and photocoagulation. The number of microaneurysms in each eye was recorded. Results. The changes between diagnosis and later photographs were analysed in 2424 patients at 6 years, 1236 at 9 years and 414 at 12 years. Of the 2424 patients studied in the 6 year cohort 1809 had either no retinopathy or microaneurysms only at entry. In these patients the presence of microaneurysms alone and also the number of microaneurysms had a high predictive value for worsening retinopathy at 3, 6, 9, and 12 years after entry into the study (e. g. at 6 years χ 2 for trend = 75 on 1 df, p 〈 0.001). The predictive value of the presence or absence of microaneurysms and their number at 3 years from diagnosis and subsequent worsening retinopathy was similar to that at entry. Conclusion/interpretation. Microaneurysms are important lesions of diabetic retinopathy and even one or two microaneurysms in an eye should not be regarded as unimportant. [Diabetologia (1999) 42: 1107–1112]
    Type of Medium: Electronic Resource
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