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| 2. |
- Agardh, Carl David, et al.
(författare)
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Effects of inhibition of glycation and oxidative stress on the development of diabetic nephropathy in rats.
- 2002
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Ingår i: Journal of Diabetes and its Complications. - 1873-460X. ; 16:6, s. 395-400
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Tidskriftsartikel (refereegranskat)abstract
- We investigated whether aminoguanidine (AG), an inhibitor of advanced glycated end product formation, or probucol (PB), a free radical scavenger, could influence signs of glomerular and distal tubular function and morphological changes in kidneys of male Wistar rats after 6 months of streptozocin (STZ)-induced diabetes. Diabetic rats had a higher kidney weight/body weight ratio (P<.001), but neither AG nor PB influenced the increased ratio. Diabetes caused an increased urinary albumin excretion (P<.05), which was normalized by AG, but further exaggerated by PB (P<.001). Diabetes also caused an increase in the urinary excretion of Tamm–Horsfall protein (P<.001). Both AG and PB attenuated this increase (P<.05 for both). A few glomeruli displayed focal thickening of varying degrees. Silver staining disclosed the glomerulopathy to be intercapillary glomerulosclerosis. Rats on PB-enriched diet displayed less pronounced changes than untreated rats (P<.01), while AG had no effect. The results suggest that oxidative stress could be involved in the development of diabetic nephropathy.
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| 3. |
- Agardh, Carl-David, et al.
(författare)
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Long-standing hyperglycemia in C57BL/6J mice does not affect retinal glutathione levels or endothelial/pericyte ratio in retinal capillaries
- 2000
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Ingår i: Journal of Diabetes and its Complications. - 1873-460X. ; 14:3, s. 146-153
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Tidskriftsartikel (refereegranskat)abstract
- Free radicals have been suggested to play a role in the development of diabetic retinopathy. The aim of the present study was to examine whether the metabolic perturbations caused by high-fat feeding of two strains of mice, the C57BL6/J mice and the NMRI mice, interfere with one of the free radical enzyme defense systems in the retina, i. e., glutathione (GSH), and whether morphological changes occur in the retinal vessels. C57BL/6J mice and NMRI mice were fed a high-fat diet (55%) for 18 months. High-fat fed mice of both strains developed overweight, hyperinsulinemia, and hyperlipidemia. In addition, the high-fat fed C57BL/6J mice also developed sustained hyperglycemia for at least 15 months. The C57BL/6J mice had lower retinal GSH levels than the NMRI mice, both when given a normal diet (29.6+/-1.2 vs. 37.1+/-1.4 nmol/mg protein; p<0.01) and when given a high-fat diet (27.0+/-1.6 vs. 34.7+/-2.6 nmol/mg protein; p<0.05). Despite the long-standing hyperglycemia, hyperinsulinemia and hyperlipidemia in the C57BL/6J mice, high-fat feeding did not cause any changes in the retinal tissue levels of GSH (27.0+/-1.6 vs. 29. 6+/-1.2 nmol/mg protein) or cysteine (7.61+/-0.63 vs. 6.80+/-0.59 nmol/mg protein). Similarly, high-fat feeding did not affect retinal GSH or cysteine levels in NMRI mice. No light microscopical retinal vessel changes were seen, either in C57BL/6J or in NMRI mice. The study therefore shows that long-standing metabolic perturbations induced by dietary obesity do not induce signs of retinopathy in two different strains of mice. Further studies are needed to explore whether this is explained by increased expression of protecting systems making these strains of mice resistant to effects of oxidative stress.
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| 4. |
- Agardh, Elisabet, et al.
(författare)
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Diabetic retinopathy
- 2004
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Ingår i: International textbook of diabetes mellitus. - Chichester, UK : John Wiley & Sons, Ltd. - 0471486558 ; , s. 1187-1187
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Diabetic retinopathy is the most common cause of blindness in the Western world in people aged 65 years or less. Intensive blood glucose control reduces the risk for development and progression of retinopathy. There is also a strong association between hypertension and retinopathy, and antihypertensive treatment seems to reduce the risk for both development and progression of retinopathy. The retinal vascular changes may vary from occasional hemorrhages and microaneurysms, to multiple hemorrhages and microaneurysms, prominent retinal thickening and exudates along blood vessels and in the macular region, new vessels, fibrosis, and retinal detachment. Sight-threatening lesions may well be present without disturbed visual function and visual outcome is dependent on timely treatments like laser photocoagulation and vitrectomy. Therefore, regular screening for diabetic retinopathy is of utmost importance. The molecular pathophysiology of diabetic retinopathy includes factors that initiate and promote the vascular disease like hyperglycemia, the polyol pathway, nonenzymatic glycation, oxidative stress, activation of protein kinase C, different growth factors, and vasoactive hormones. Several changes also take place in the retinal vasculature, which cause changed retinal blood flow and heterogeneity of its distribution, areas of nonperfusion and ischemia and hypoxia, which in turn leads to an increased production of vasoactive factors like vascular endothelial growth factor.
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| 5. |
- Agardh, Elisabet, et al.
(författare)
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Effects of inhibition of glycation and oxidative stress on the development of cataract and retinal vessel abnormalities in diabetic rats
- 2000
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Ingår i: Current Eye Research. - 0271-3683. ; 21:1, s. 543-549
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To study effects of inhibition of glycation, and oxidative stress on the development of cataract and retinal vessel abnormalities in diabetic rats. METHODS: Diabetes was induced in male Wistar rats with streptozocin (STZ; 60 mg/kg BW, i.p.). Diabetic as well as strain matched control rats were fed 1) a normal diet, 2) addition of aminoguanidine in the drinking water (0.5 g/l for diabetic rats and 1.0 g/l for control rats) or 3) probucol in the pellets (1% w/w). After 6 months, the number of acellular vessels, endothelial cells and pericytes were counted in trypsin digested retinal vessel preparations, and the total retinal tissue amount of glutathione (GSH) and cysteine was measured with HPLC. RESULTS: Cataract formation occurred after 13 weeks in diabetic animals compared with 17 weeks for those treated with aminoguanidine, and 16 weeks for those treated with probucol (p < 0.001 in both cases). Aminoguanidine inhibited the formation of acellular collapsed capillary strands, 9 (3-14) vs. 18 (12-262) (median, range) per quadrant in untreated diabetic rats (p = 0.004), while probucol did not have any effect. Neither aminoguanidine, nor probucol influenced the endothelial/pericyte ratio. Diabetes caused a reduction in the GSH/cysteine ratio (10.7 +/- 0.6 vs. 15.3 +/- 1. 5) (mean +/- SD; p < 0.001). Probucol partly restored this imbalance (p < 0.05) whereas aminoguanidine did not. CONCLUSIONS: The results indicate that cataract formation in diabetes involves both glycation and oxidative stress processes. The reduced formation of acellular collapsed capillary strands by aminoguanidine suggests a potential role for glycation in vascular damage. The positive effect of probucol on cysteine/GSH metabolism imbalance indicates that derangements of one of the retinal defense systems against oxidative stress can be normalized by antioxidants.
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| 6. |
- Agardh, Elisabet, et al.
(författare)
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Fetal growth is not associated with early onset of severe retinopathy in type 1 diabetes mellitus
- 2000
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Ingår i: Diabetes Research and Clinical Practice. - 1872-8227. ; 48:1, s. 61-65
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Tidskriftsartikel (refereegranskat)abstract
- Reduced fetal growth has been suggested as a possible risk factor for diabetic nephropathy. The aim of the present study was to examine whether there could be an association also with rapidly progressing severe retinopathy in younger type 1 diabetic patients. Maternal pregnancy, as well as birth parameters of 27 type 1 diabetic patients with severe retinopathy diagnosis at a median age of 25 years, were studied retrospectively. The control group consisted of 22 type 1 diabetic patients with mild background retinopathy and with similar age, age at onset, and duration of diabetes. Mothers of the subjects with severe retinopathy had a higher body mass index (P = 0.03) but similar age, blood pressure levels, and weight gain during pregnancy as those of the control group. All but four babies, two in each group, were born after 37 completed gestational weeks. There were no differences regarding birth weight or of relative birth weight corrected for gestational length. Head circumference, birth length, and placenta weight were similar. The results indicate that fetal growth is not a factor of major importance for the development of severe retinopathy in younger type 1 diabetic patients.
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| 7. |
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| 8. |
- Agardh, Elisabet, et al.
(författare)
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Retinal glial cell immunoreactivity and neuronal cell changes in rats with STZ-induced diabetes
- 2001
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 23:4, s. 276-284
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To study whether diabetes could influence glial cells, retinal neurons, and pigment epithelial cells and if so, to evaluate whether any changes could be influenced by aminoguanidine (AG) or probucol (PB). METHODS: Streptozocin (STZ)-induced diabetic male Wistar rats and age-matched control rats were fed a normal diet, addition of AG in the drinking water (0.5 g/l for diabetic and 1.0 g/l for control rats) or PB in the pellets (1 % w/w) for one or six months. Paraffin embedded retinal sections were incubated in the primary antibodies GFAP, calbindin, RPE65, and Hu, for glial, horizontal, pigment epithelial, and ganglion cells, respectively, and in fluorescent secondary antibodies. RESULTS: One month after STZ injection, GFAP immunoreactivity was sparse, but after six months it was prominent in glial cells in 5/5 diabetic and 1/7 control retinas (p = 0.015). Neither AG, nor PB influenced this immunoreactivity. Numbers of retinal pigment epithelial cells and cells in the ganglion cell layer, were similar at one and six months of diabetes. By time, the number of horizontal cells decreased (p < 0.001) and branching and numbers of their terminals were reduced (p < 0.001). CONCLUSION: Diabetes for six months resulted in increased glial cell immunoreactivity, and by age, horizontal cell numbers and branching of their terminals decreased, morphological patterns that were unaffected by AG or PB. The numbers of retinal pigment epithelial cells and cells in the ganglion cell layer were unaffected both by age and diabetes.
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| 9. |
- Agardh, Elisabet, et al.
(författare)
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Severe retinopathy in type 1 diabetic patients is not related to the level of plasma homocysteine
- 2000
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 60:3, s. 169-174
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Tidskriftsartikel (refereegranskat)abstract
- The vascular-injuring amino acid homocysteine was previously shown to be increased in plasma in type 1 diabetic patients with clinical signs of nephropathy. Previous studies have also shown an inconsistent relationship between the development of diabetic nephropathy and retinopathy, indicating different pathogenetic mechanisms. In this study, plasma homocysteine was measured in 25 type 1 diabetic patients with a well-characterized form of severe retinopathy. Furthermore, a group of 24 type 1 diabetic patients with similar age at onset of diabetes and diabetes duration with no or minimal background retinopathy were investigated, in order to determine whether plasma homocysteine levels are different from those in patients with severe retinopathy. Patients with severe retinopathy did not have higher plasma levels of homocysteine (13.9 micromol/L; 5.9-30.7, median and range) than those without retinopathy (10.4 micromol/L; 5.7-18.9). Within the group of patients with severe retinopathy, increased homocysteine levels were confined to the patients (19.9 micromol/L; 10.0-30.7, n=9) with serum creatinine levels > 100 micromol/L, compared to those patients (9.6; 5.9-14.3 micromol/L, n=15) with a serum creatinine below 100 micromol/L. None of the patients without or with minimal background retinopathy had serum creatinine levels > 100 micromol/L. We conclude that diabetic retinopathy is not associated with increased plasma homocysteine levels, but plasma homocysteine accumulates, probably owing to reduced glomerular filtration, in diabetic patients with signs of nephropathy. In these patients, the promoting effect of nephropathy on the development of retinopathy does not seem to be mediated through homocysteine.
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| 10. |
- Agardh, Elisabet, et al.
(författare)
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Ögon
- 2002
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Ingår i: Diabetes. - 9147048999 ; , s. 236-236
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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