1.
Agardh, Carl-David, et al.
(författare)
Lack of association between plasma homocysteine levels and microangiopathy in type 1 diabetes mellitus
1994
Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 54:8, s. 637-641
Tidskriftsartikel (refereegranskat) abstract
The reactive vascular-injuring amino acid homocysteine was previously shown to be increased in plasma in diabetic patients with clinical signs of nephropathy. In this study, plasma homocysteine was measured in type 1 diabetic patients with normoalbuminuria (n = 22), microalbuminuria (n = 40) and proteinuria (n = 14) in order to investigate whether plasma homocysteine levels are increased already at the stage of incipient nephropathy, i.e. microalbuminuria. Furthermore, patients were characterized according to the degree of retinopathy. Plasma homocysteine in the whole population (n = 76) was related to B-Folate (r = 0.38, p < 0.01), S-Creatinine (r = 0.55, p < 0.001), S-Urea (r = 0.37, p < 0.01), U-Albumin (r = 0.46, p < 0.001), urinary N-acetyl-beta- glucosaminidase (r = 0.40, p < 0.001), systolic blood pressure (r = 0.36, p < 0.01) and diabetes duration (r = 0.44, p < 0.001). There were no differences in plasma homocysteine levels between patients with normoalbuminuria (8.0 +/- 1.7 mumol l-1; mean +/- SD) and those with microalbuminuria (9.1 +/- 3.4 mumol l-1). However, patients with clinical signs of nephropathy had higher plasma homocysteine levels (12.9 +/- 5.7 mumol l-1, p < 0.01) compared to the other two groups. There was no association between plasma homocysteine levels and different degrees of retinopathy. Thus, the present study does not show any relation between plasma homocysteine levels and early stages of diabetic nephropathy or retinopathy indicating that elevated concentrations of plasma homocysteine does not explain the increased risk for atherosclerosis observed in patients with microalbuminuria.
2.
Agardh, Carl-David, et al.
(författare)
Serum beta-hexosaminidase in diabetes mellitus with reference to the type of treatment
1982
Ingår i: Acta Medica Scandinavica. - 0001-6101. ; 212:1-2, s. 39-41
Tidskriftsartikel (refereegranskat) abstract
A significantly increased serum level of beta-hexosaminidase was found in an unselected group of 85 diabetics. When the patients were divided into three groups according to type of treatment, increased enzyme levels were found only in patients treated with oral hypoglycemic agents or diet while insulin-treated patients had normal serum levels of beta-hexosaminidase. There was a positive correlation between beta-hexosaminidase and blood glucose concentration for the entire patient series. When grouped according to treatment, a positive correlation was found only in the insulin-treated group despite its normal serum activity of beta-hexosaminidase. Serum beta-hexosaminidase of patients with retinopathy did not differ from the mean value of their group. It is concluded that the activity of beta-hexosaminidase in diabetics can produce different results depending on the type of patients under study.
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.
Arnadottir, M, et al.
(författare)
The effect of reduced glomerular filtration rate on plasma total homocysteine concentration
1996
Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 56:1, s. 41-46
Tidskriftsartikel (refereegranskat) abstract
The concentration of homocysteine in plasma has been shown to be increased in renal failure, possibly contributing to the accelerated atherosclerosis observed in uraemic patients. The aim of the present study was to document the relationship between plasma total homocysteine (tHcy) concentrations and glomerular filtration rates (GFR) in highly selected patients, with renal function ranging from normal to dialysis dependency. GFR was defined as the plasma clearance of iohexol; a more accurate method than the creatinine-based estimations applied in previous studies. Plasma tHcy concentrations were highly correlated to GFR (r = -0.70, p < 0.0001) and were significantly increased already in moderate renal failure. According to a multiple regression analysis, GFR and red cell folate concentrations independently predicted plasma tHcy concentrations, whereas those of serum creatinine, plasma pyridoxal-5-phosphate, urine albumin and urine alpha-1-microglobulin (a marker of tubular damage) did not. Thus, GFR seems to be a better determinant of plasma tHcy concentration than serum creatinine concentration. Plasma total cysteine and total cysteinylglycine concentrations followed the same pattern as those of tHcy.
5.
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.
6.
Hultberg, Björn, et al.
(författare)
Homocystein--markör för kärlsjukdom hos aldre med psykisk sjukdom.
2008
Ingår i: Läkartidningen. - 0023-7205. ; 105:38, s. 2576-2578
Forskningsöversikt (refereegranskat) abstract
Many studies have reported higher total plasma homocysteine (tHcy) in elderly patients with mental illness than in control subjects. There are many different determinants of plasma tHcy concentration, including age, cobalamin/folate status, renal function and the presence of vascular disease. The presence of vascular disease may contribute to cognitive impairment. We have investigated elderly patients with regard to plasma tHcy and the presence of vascular disease. Clarification of the role of vascular risk factors in mental illness is important because most are modifiable, in contrast to other risk factors such as age and genetics. The main findings in our studies imply that elevated plasma tHcy concentration in elderly patients with mental illness is mainly associated with the presence of vascular disease and is not related to the specific psychogeriatric diagnosis. Furthermore, it seems possible that the control of conventional vascular risk factors could be guided by the level of plasma tHcy, serum cystatin C, and serum N-terminal pro-brain natriuretic peptide. Patients with an elevation of any of these parameters could be selected for a lower target level of vascular risk factors such as blood pressure cholesterol etc. than conventional target levels.
7.
Hultberg, Björn, et al.
(författare)
Increased levels of plasma homocysteine are associated with nephropathy, but not severe retinopathy in type 1 diabetes mellitus
1991
Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 51:3, s. 277-282
Tidskriftsartikel (refereegranskat) abstract
The reactive vascular-injuring amino acid homocysteine was measured in plasma samples from 79 well-characterized type 1 diabetic patients and 46 control subjects. Patients with proliferative retinopathy had higher homocysteine levels (15.0 +/- 6.3 mumols l-1; mean +/- SD, p less than 0.001; n = 42) than those with progressive retinopathy during a two-year period (10.4 +/- 1.6 mumols l-1; n = 12), no or minimal retinopathy (10.7 +/- 4.3 mumols l-1; n = 25), and the control subjects (11.0 +/- 3.4 mumols l-1). Within the group of patients with proliferative retinopathy increased homocysteine levels were confined to those patients that had serum creatinine levels greater than 115 mumols l-1 and/or an albumin:creatinine clearance ratio greater than or equal to 0.02 x 10(-3) (17.0 +/- 5.9 mumols l-1; n = 23), whereas those with no or only minimal nephropathy had levels (12.1 +/- 5.5 mumols l-1; n = 18) that were not different from the control group. We conclude that neither type 1 diabetes mellitus nor diabetic retinopathy per se is associated with increased plasma homocysteine levels. In contrast, homocysteine accumulates, probably owing to reduced glomerular filtration, in diabetic patients with advanced nephropathy. This suggests that homocysteine might contribute to the accelerated development of macroangiopathy seen especially in this subgroup of diabetic patients.
8.
Hultberg, Björn, et al.
(författare)
Interaction of metals and thiols in cell damage and glutathione distribution: potentiation of mercury toxicity by dithiothreitol
2001
Ingår i: Toxicology. - 0300-483X. ; 156:2-3, s. 93-100
Tidskriftsartikel (refereegranskat) abstract
In the present study, we have investigated the effects of extracellular redox status and metal/thiol interactions on glutathione distribution in HeLa cell cultures. No effects were seen on glutathione distribution after the addition of different thiols, whereas the pro-oxidant copper ions affected glutathione distribution in several ways. The addition of dithiothreitol (DTT) but not the other thiols potentiated the effects of mercury ions on glutathione distribution and cell toxicity. In the presence of DTT, increased intra- and extracellular glutathione concentrations were noted already at 0.05 micromol/l, which was below the previously reported toxicity threshold for mercury ions in blood. Likewise DTT potentiated the effects of copper ions on glutathione distribution and cell toxicity, whereas the addition of DTT to cell cultures with a non-metal thiol reactive agent (hydroquinone) or an oxidative agent (hydrogen peroxide) did not affect glutathione distribution or cell toxicity. Thus, it seems as the synergistic effects between DTT and thiol reactive agents only apply to metal ions.
9.
Hultberg, Björn, et al.
(författare)
Lipoic acid increases glutathione production and enhances the effect of mercury in human cell lines.
2002
Ingår i: Toxicology. - 0300-483X. ; 175:1-3, s. 103-110
Tidskriftsartikel (refereegranskat) abstract
Thiols are known to influence the metabolism of glutathione. In a previous study (Toxicology 156 (2001) 93) dithiothreitol (DTT) did not show any effect on intra- or extracellular glutathione concentrations in HeLa cell cultures but increased the effects of mercury ions on glutathione concentrations, whereas monothiols such as N-acetylcysteine (NAC) or glutathione did not. In the present study, we have investigated the effects of thiols as well as the interaction between thiols and mercury ions in cultures of both HeLa and hepatoma cells. Furthermore, we have added alpha-lipoic acid (LA) to the previously used test panel of thiols, since it is metabolised intracellularly to a dithiol (dihydrolipoate). The present study shows that LA increased intra- and extracellular concentrations of glutathione in both HeLa and hepatoma cell cultures. In contrast to results for HeLa cells, the presence of DTT increased the intracellular glutathione concentration in hepatoma cells. No increase of glutathione concentrations was observed in hepatoma cell cultures in the presence of the monothiols (NAC, homocysteine or glutathione) tested, in agreement with previous findings in HeLa cell cultures. The presence of dithiols, either DTT or dihydrolipoate (the metabolite of LA), increased the effects of mercury ions on glutathione concentrations in hepatoma cells, whereas monothiols such as NAC or glutathione did not, in agreement with previous findings in HeLa cells. Thus, metabolic effects of mercury ions were observed in hepatoma cells as well as in HeLa cells at a lower concentration than the supposed toxicity threshold for mercury in blood.
10.
