| 1. |
|
|
| 2. |
- Agardh, Carl-David, et al.
(författare)
-
Long-standing hyperglycemia in C57BL/6J mice does not affect retinal glutathione levels or endothelial/pericyte ratio in retinal capillaries
- 2000
-
Ingår i: Journal of Diabetes and its Complications. - 1873-460X. ; 14:3, s. 146-153
-
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.
|
|
| 3. |
- Agardh, Elisabet, et al.
(författare)
-
Severe retinopathy in type 1 diabetic patients is not related to the level of plasma homocysteine
- 2000
-
Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 60:3, s. 169-174
-
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.
|
|
| 4. |
- Andersson, Anders, et al.
(författare)
-
Hyperhomocysteinemia and changed plasma thiol redox status in chronic obstructive pulmonary disease
- 2001
-
Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621. ; 39:3, s. 229-233
-
Tidskriftsartikel (refereegranskat)abstract
- Reduced and total homocysteine, cysteine, glutathione and cysteinylglycine in plasma were investigated in 19 patients with chronic obstructive pulmonary disease and in 29 healthy subjects. The purpose was to examine the influence of pro-oxidant activity caused by the lung disease on the metabolism of homocysteine and other plasma thiols. We observed a decreased concentration of reduced glutathione and a decreased ratio of reduced/total glutathione in the patients compared to the healthy individuals, which supports the hypothesis of an association between free radicals and pathogenesis in some lung diseases. We also observed an increased total plasma homocysteine. The influence of a possible extracellular pro-oxidant activity on the concentration of total plasma homocysteine is discussed.
|
|
| 5. |
- Andersson, Anders S, et al.
(författare)
-
Vitamin supplementation normalizes total plasma homocysteine concentration but not plasma homocysteine redox status in patients with acute coronary syndromes and hyperhomocysteinemia.
- 2002
-
Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621. ; 40:6, s. 554-558
-
Tidskriftsartikel (refereegranskat)abstract
- Despite the growing evidence that elevated total homocysteine (tHcy) in plasma is a cardiovascular risk factor, the mechanism underlying the vascular injury is still unknown. Studies are difficult due to the fact that little is known about the formation of different homocysteine species in vivo. In the present study we have investigated the different fractions of tHcy in 21 patients with acute coronary syndromes and elevated concentration of plasma tHcy. A subgroup of the patients (n=16) was investigated before and after a 3 months study period with or without vitamin supplementation (folic acid 5 mg, pyridoxine 40 mg and cyanocobalamin 1 mg once daily). A major finding is that these patients had a lowered ratio (0.95%) between the concentration of reduced homocysteine (HcyH) and tHcy compared to controls (1.38%). A low ratio HcyH/tHcy in plasma in combination with elevated plasma tHcy concentrations might reflect increased oxidative activity or decreased reducing capacity in plasma from the patients. Another main finding in the present study is that, although vitamin supplementation of these patients normalized plasma tHcy, the ratio between HcyH and tHcy did not normalize. Since substantial evidence indicates that progression of arteriosclerosis is related to enhanced oxidant activity, the premature vascular disease associated with increased plasma tHcy concentration might be due to increased oxidative activity and the elevated plasma tHcy concentration may only reflect the increased oxidative stress.
|
|
| 6. |
- Arnadottir, Margret, et al.
(författare)
-
Homocysteine and nephrotic syndrome - Reply
- 2001
-
Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 16:8, s. 1721-1721
-
Tidskriftsartikel (refereegranskat)
|
|
| 7. |
- Arnadottir, Margret, et al.
(författare)
-
Plasma total homocysteine concentration in nephrotic patients with idiopathic membranous nephropathy
- 2001
-
Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 16:1, s. 45-47
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The atherothrombotic risk pattern of the nephrotic syndrome resembles that of hyperhomocysteinemia. However, the effect of nephrotic range proteinuria on homocysteine metabolism has never been studied. METHODS: The study included 11 male nephrotic patients with idiopathic membranous nephropathy who underwent a treatment trial with adrenocorticotrophic hormone and 11 male non-nephrotic, renal function-matched control subjects. The nephrotic patients were studied before and after the treatment, which induced a marked reduction in urinary protein excretion and a moderate improvement in renal function in all cases. RESULTS: Plasma total homocysteine (tHcy) concentration did not change significantly during treatment, whereas the nephrotic patients had significantly lower tHcy than the non-nephrotic patients (14.2 +/- 3.4 micromol/l vs 19.0 +/- 5.4 micromol/l). tHcy correlated significantly with serum concentrations of creatinine (r = 0.53, P < 0.05) and albumin (r = 0.43, P < 0.05), glomerular filtration rates (GFRs) (iohexol clearances) (r = -0.42, P < 0.05) and urinary albumin excretion (r = -0.47, P < 0.05). CONCLUSION: The expected tHcy-lowering effect of improved renal function may have masked a tHcy-elevating effect due to reduced proteinuria leading to no net change in tHcy during treatment. The notion of an increase in tHcy associated with remission of the nephrotic syndrome is in accordance with the significantly lower tHcy in the nephrotic renal patients compared with the non-nephrotic renal function-matched patients, and the relationships between tHcy and serum albumin concentrations as well as urinary albumin excretion. Thus, the results of this small study suggest that nephrotic range proteinuria directs homocysteine metabolism towards a decrease in tHcy. However, the findings need to be confirmed in larger patient populations and in different varieties of the nephrotic syndrome.
|
|
| 8. |
- Arnadottir, M, et al.
(författare)
-
The effect of vitamin B-12 on total plasma homocysteine concentration in folate-replete hemodialysis patients
- 2003
-
Ingår i: Clinical Nephrology. - 0301-0430. ; 59:3, s. 186-189
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: Results from several studies indicate that the total homocysteine (tHcy) concentration in plasma is an independent risk factor for cardiovascular disease in hemodialysis patients. Folic acid is the established mainstay of homocysteine-lowering treatment, but since such treatment does not normalize plasma tHcy concentration in hemodialysis patients, it is of importance to search for additional therapy. Methods: Twenty-eight folate-replete hemodialysis patients were randomized to 2 equally sized groups, a treatment group and a control group. The treatment group received vitamin B 12 tablets at a dose of 2 mg 3 times a week for 6 weeks (after each dialysis session) while the control group received no such treatment. Blood samples were collected before and at the end of the treatment period for analysis of tHcy in plasma and vitamin B-12, methylmalonic acid as well as folate in serum. Results: At the end of the study period, serum vitamin B12 concentrations were significantly higher in the treatment group than in the control group. Plasma tHcy concentrations decreased significantly in both groups during the study period. However, there was no difference between the responses of the 2 groups. Conclusion: The results of this open, randomized controlled study did not support the hypothesis that treatment with oral vitamin B12 has considerable homocysteine-lowering effect in folate-replete hemodialysis patients.
|
|
| 9. |
- Arnadottir, Margret, et al.
(författare)
-
The postdialytic rise in the plasma total homocysteine concentration is delayed
- 2002
-
Ingår i: Blood Purification. - : S. Karger AG. - 0253-5068 .- 1421-9735. ; 20:4, s. 334-337
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: The mechanism behind the uremic hyperhomocysteinemia has not been elucidated. Possibly, dialyzable uremic toxins play a role, e.g. as enzyme inhibitors. If so, the conditions for enzymatic removal would be expected to improve after dialysis. Therefore, we studied the postdialytic pattern of the plasma total homocysteine (tHcy) concentration. METHODS: We collected blood samples from 19 stable, vitamin-supplemented hemodialysis patients before and at 5, 60, as well as at 480 min after a dialysis session. The patients were studied after dialysis with a low-flux dialyzer (Polyflux 6L) and a high-flux dialyzer (Polyflux 14S). RESULTS: The mean predialytic plasma tHcy concentration was 13.3 micromol/l which is considerably lower than the concentrations observed in our previous studies. In all patients, the plasma tHcy concentration fell during treatment with both types of dialyzers (average decrease 28 +/- 7%, p < 0.0001, and 31 +/- 8%, p < 0.0001, respectively). No postdialytic change in the plasma tHcy concentration was observed at 60 min after low-flux dialysis, however, after high-flux dialysis, the plasma tHcy concentration was significantly lower at 60 min postdialysis than at 5 min (3 +/- 8%, p < 0.05). At 480 min after dialysis, a significant postdialytic increase in the plasma tHcy concentration was found (6 +/- 9%, p < 0.01, and 11 +/- 5%, p < 0.0001, respectively) both in the case of low-flux and high-flux treatment. CONCLUSION: In the postdialytic phase, we observed a short-lived stability in the plasma tHcy concentration, and in the case of high-flux dialysis, even a slight decrease in the plasma tHcy concentration. The results support the hypothesis that dialyzable substances interfere with homocysteine removal.
|
|
| 10. |
|
|
