| 1. |
- Agardh, Carl-David, et al.
(författare)
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Glutathione levels are reduced in diabetic rat retina but are not influenced by ischemia followed by recirculation
- 1998
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Ingår i: Metabolism, Clinical and Experimental. - 1532-8600. ; 47:3, s. 269-272
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Tidskriftsartikel (refereegranskat)abstract
- Free radicals have recently been proposed to play a role in the development of diabetic retinopathy. The aim of the present study was to examine whether the abnormal metabolism caused by diabetes and by ischemia followed by recirculation interferes with a free radical enzyme defense system in the retina, ie, glutathione. Diabetes mellitus was induced by injecting streptozotocin ([STZ] 60 mg/kg body weight [BW] intraperitoneally). After 2 and 6 months, respectively, glutathione levels were measured in the retina and compared against those of age-matched normal control rats. Retinal ischemia was induced by careful ligation of the vessels and the accompanying optic nerve behind the left eye bulb. The right eye served as a control. After 90 minutes of ischemia, retinal circulation was reestablished by removing the ligature. Two-month-old diabetic rats were kept for an additional 3 days and normal rats for 5 minutes, 15 minutes, or 3 days before they were killed for measurement of glutathione. Retinal levels of glutathione were significantly lower in 6-month diabetic compared with 2-month diabetic rats (16.6 +/- 2.9 v 19.0 +/- 2.2 nmol/mg protein, P < .05) and 6-month normal control rats (16.6 +/- 2.9 v 21.0 +/- 2.1 nmol/mg protein, P < .001). Ischemia followed by recirculation did not influence the total tissue level of glutathione either in 2-month-old diabetic rats or in normal rats. The present study indicates that the abnormal metabolism caused by diabetes, rather than by changes in retinal circulation, results in an impaired defense mechanism against free radicals, a factor that may be of importance for the development of diabetic retinopathy. However, since glutathione levels in the present study were measured in the whole retina, it cannot be excluded that particular cell types, such as vascular cells, show an alteration in glutathione that is masked by the glutathione levels in the other nonvascular cells of the retina. Studies using other techniques are needed to further explore this subject.
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| 2. |
- Agardh, Carl-David, et al.
(författare)
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The glutathione levels are reduced in Goto-Kakizaki rat retina, but are not influenced by aminoguanidine treatment
- 1998
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 17:3, s. 251-256
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To examine the levels of the free radical protecting enzyme glutathione and the endothelial/pericyte ratio in retinal capillaries in the Goto-Kakizaki (GK) Wistar rat, with and without aminoguanidine treatment. METHODS: Eight-month-old GK rats, with non-obese, spontaneous non-insulin-dependent diabetes mellitus (NIDDM), were examined after a six month period of aminoguanidine treatment. Glutathione levels were measured with high performance liquid chromatography and the endothelial/pericyte ratio was calculated in trypsin digested vessel preparations. RESULTS: The levels of glutathione in GK rat retina were significantly lower compared to controls (p = 0.0108). There was no difference in the endothelial/pericyte ratio compared to matched control rats (1.8 +/- 0.2 vs. 1.8 +/- 0.1, respectively). Aminoguanidine treatment did not influence either the degree of hyperglycemia, the levels of glutathione or the endothelial/pericyte ratio in GK or control rat retina. CONCLUSIONS: The results indicate that impaired glucose metabolism may influence one of the defense mechanisms for oxidative stress, but also suggest that decreased glutathione levels occur prior to morphological signs of pericyte loss and/or endothelial cell proliferation in this animal model of hereditary NIDDM.
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| 3. |
- Arnadottir, Margret, et al.
(författare)
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Hyperhomocysteinemia in cyclosporine-treated renal transplant recipients
- 1996
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Ingår i: Transplantation. - 1534-6080. ; 61:3, s. 509-512
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Tidskriftsartikel (refereegranskat)abstract
- Moderate hyperhomocysteinemia, an independent cardiovascular risk factor, has been reported in renal transplant recipients. In the present study, plasma concentrations of total homocysteine were significantly increased in 120 renal transplant recipients as compared with 60 healthy controls (19.0 +/- 6.9 vs. 11.6 +/- 2.8 mumol/L, P < 0.0001) and as compared with 53 patients without a transplant but with a comparable degree of renal failure (19.0 +/- 6.9 vs. 16.0 4.9 mumol/L, P < 0.01). There was a significant inverse correlation between glomerular filtration rates and plasma homocysteine concentrations in the renal transplant recipients (r = -0.52, P < 0.0001). Groups of renal transplant recipients, with and without cyclosporine, and renal patients without a transplant were studied; these groups were comparable regarding age, sex distribution, glomerular filtration rate, and folate and vitamin B12 concentrations. Renal transplant recipients on cyclosporine had significantly higher plasma homocysteine concentrations than those not on cyclosporine (19.5 +/- 7.6 vs. 16.2 +/- 4.8 mumol/L, P < 0.05), and the patients without a transplant (19.5 +/- 7.6 vs. 16.0 +/- 4.9 mumol/L, P < 0.01). Thus, the hyperhomocysteinemia of renal transplant recipients not treated with cyclosporine, and that of renal patients without a transplant probably is explained by the same mechanism: renal insufficiency. An additional mechanism seems to operate in renal transplant recipients treated with cyclosporine. The lack of correlation between the concentrations of plasma homocysteine and red cell folate in these patients suggests that cyclosporine interferes with folate-assisted remethylation of homocysteine. Plasma homocysteine concentrations were significantly increased in 24 patients with a history of atherosclerotic complications as compared with the remaining 96 renal transplant recipients (20.8 +/- 4.4 vs. 18.5 +/- 7.3 mumol/L, P < 0.01).
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| 4. |
- Arnadottir, M, et al.
(författare)
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The effect of reduced glomerular filtration rate on plasma total homocysteine concentration
- 1996
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 56:1, s. 41-46
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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.
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| 5. |
- Frennby, Bo, et al.
(författare)
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The use of iohexol clearance to determine GFR in patients with severe chronic renal failure - a comparison between different clearance techniques
- 1995
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Ingår i: Clinical Nephrology. - 0301-0430. ; 43:1, s. 35-46
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Tidskriftsartikel (refereegranskat)abstract
- The nonionic low-osmolar contrast medium iohexol was used as marker of glomerular filtration rate (GFR) in 53 patients with stable renal function (group I: n = 32, group II: n = 21). All the patients had clearance values < or = 30 ml.min-1.1.73 m-2 body surface; 40 patients < 20 ml.min-1.1.73 m-2 body surface. Simultaneous determinations of renal clearance and plasma clearance, both as slope clearance and single sample clearance, were performed after intravenous injection of 10 ml iohexol 300 mg iodine/ml. In groups I and II plasma was sampled early (around 3 hours) and late (up to 24 hours) after the injection. In group I urine was collected during four 40-minute periods and in group II during one 3-hour period and in group II the residual urine was estimated by ultrasound. Plasma and urine iodine concentrations were analyzed with X-ray fluorescence technique (Reanalyzer PRX90, Provalid AB, Sweden). In group II S-creatinine and tubular function test were followed to detect any signs of nephrotoxicity. In 6 anuric patients (group III) 10 ml iohexol 300 mg I/ml was injected to assess its extrarenal clearance. In groups I and II the slope clearance correlated excellently with the single sample clearance (r = 0.99) when a late plasma sample was used in both techniques. In group II, where residual urine was estimated by ultrasound, renal clearance correlated better with slope clearance than in group I (r = 0.94 vs r = 0.89). There were no signs of nephrotoxicity in the parameters noted. In group III, extrarenal plasma clearance of iohexol did not exceed 2 ml.min-1.1.73 m-2. CONCLUSION: GFR < 20 ml/min can accurately and safely be determined as renal clearance or plasma clearance of iohexol after an intravenous dose of 10 ml 300 mg I/ml. Plasma clearance techniques, which have the practical clinical advantage of no urine sampling, do at low GFR require a late plasma sample taken, for instance, 24 hours after injection of iohexol, irrespective of whether slope technique or single sample technique or one-compartment or poly-compartment models are used.
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| 6. |
- Hauge, Truls, et al.
(författare)
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Gamma-Glutamyl Transferase, Intestinal Alkaline Phosphatase and Beta-Hexosaminidase Activity in Duodenal Biopsies from Chronic Alcoholics
- 1998
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Ingår i: Hepatogastroenterology. ; 45:22, s. 985-989
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: Gamma-glutamyl transferase (GGT) and intestinal alkaline phosphatase (IAP) are present in the brush border of mucosal absorptive cells in the small intestine. There are few studies on the effect of alcohol consumption on these enzymes. Increased intestinal GGT in biopsy specimens from the duodenum has been described in chronic alcoholics. In experimental animals alcohol effects varies with duration of exposure and with nutritional factors.METHODOLOGY: IAP, GGT and the lysosomal enzyme beta-hexosaminidase (Hex) were examined in duodenal biopsy specimens from 23 defined chronic alcoholics and 33 non alcoholic controls. The results were correlated to serum GGT, alkaline phosphatase, CDT (Carbohydrate Deficient Transferrin) and the villus index.RESULTS: Both the intestinal GGT (0.52 + 0.05 SEM vs. 0.30 + 0.024 SEM microkat/g protein, p<0.0001) and the IAP (22.11 + 2.49 SEM vs. 12.28 + 1.35 SEM microkat/g protein, p=0.0010) were significantly higher in alcoholics than in controls. There was no correlation between intestinal and serum alkaline phosphatase and GGT activity within the two groups.CONCLUSIONS: Chronic alcohol consumption causes increased intestinal GGT and IAP activity in man. No effect on Hex was seen. The enzyme activity in the small intestine did not correlate to serum enzyme activity or to morphological changes in the small intestine.
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| 7. |
- Hultberg, Björn, et al.
(författare)
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Concentrations of plasma methylmalonic acid in 80-year-olds show only weak relation to psychological performance
- 1999
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621. ; 37:10, s. 963-967
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Tidskriftsartikel (refereegranskat)abstract
- Most studies of the relation between psychological performance in the elderly and deficiencies of cobalamin and folate have used methods that determine the blood concentrations of these vitamins, which might not reflect the vitamin status in the tissues. Recently, two new markers, plasma homocysteine and methylmalonic acid, have attracted growing interest since they are considered to reflect the status of cobalamins and folates in the tissues. In a previous study, we noted a strong association between five parameters of well-being and lower concentrations of plasma homocysteine. In the present study, we have extended these observations by determination of plasma methylmalonic acid in the same healthy elderly population. In the present study, 18 out of 100 subjects had increased plasma methylmalonic acid and in 7 of these subjects, the concentrations of serum cobalamin, blood folate, plasma homocysteine and serum creatinine were within normal limits. The relation between plasma methylmalonic acid concentrations and concentrations of serum cobalamin and blood folates and five parameters of well-being were investigated. Concentrations of plasma methylmalonic acid were only weakly associated with the concentrations of serum cobalamin and lower scores on the logical reasoning test. The present study clearly shows that the levels of plasma methylmalonic acid show a much lesser association with the parameters of well-being than did plasma homocysteine.
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| 8. |
- Hultberg, Björn, et al.
(författare)
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Plasma beta-hexosaminidase isoenzymes A and B exhibit different relations to blood glucose levels in a population of Type 1 diabetic patients
- 1995
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 55:8, s. 723-728
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Tidskriftsartikel (refereegranskat)abstract
- The activity of lysosomal enzymes, such as beta-hexosaminidase (Hex), is increased in the plasma and serum of diabetic patients. A positive association has been shown between enzyme activity and glycated proteins, indicating an association with the degree of metabolic control. Several isoenzymes of Hex exist. Studies have reported different proportions of the isoenzymes in plasma from diabetic patients, compared with healthy subjects. In the present study, Hex isoenzymes were examined in 76 Type 1 diabetic patients, of mean age 37.4 years (SD 12.9) compared with 38 age- and sex-matched healthy control subjects in an attempt to evaluate the influence of long- and short-term changes in blood glucose levels on these isoenzymes. The results show that Hex A activity (p<0.01), but not Hex B activity, was higher in the diabetic patients. Hex A activity was positively associated with both the actual blood glucose levels (r = 0.48, p<0.001) and haemoglobin A1c (HbA1c) (r = 0.43, p<0.001), while Hex B activity was associated with the level of HbA1c only (r = 0.42, p<0.001). Both Hex A and B activities were also positively associated with early signs of diabetic nephropathy (e.g. urinary excretion of Hex, fractional albumin excretion ratio and urinary albumin). There was no association between Hex A and B activities and different degrees of retinopathy. In conclusion, the present study demonstrates an association between Hex A and B and metabolic parameters in diabetes as well as with clinical signs of early diabetic nephropathy, but no association with the degree of retinopathy. Furthermore, Hex A seems to be more influenced than Hex B by short-term changes in blood glucose levels.
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| 9. |
- Hultberg, Björn, et al.
(författare)
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Poor metabolic control, early age at onset, and marginal folate deficiency are associated with increasing levels of plasma homocysteine in insulin-dependent diabetes mellitus. A five-year follow-up study
- 1997
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - 1502-7686. ; 57:7, s. 595-600
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Tidskriftsartikel (refereegranskat)abstract
- In a previous study, we showed that diabetic patients exhibited significantly increased concentrations of total plasma homocysteine (tHcy), but not until the onset of nephropathy. It was suggested that the hyperhomocysteinaemia might contribute to the accelerated atherosclerotic process in diabetic patients. In the present study, we have analysed the main determinants of plasma homocysteine (i.e. serum cobalamin, blood folate and serum creatinine), and also some other parameters related to diabetes mellitus, such as medical history, metabolic and renal quantities, on two occasions with a 5-year interval in 50 patients with insulin-dependent diabetes mellitus, in order to further elucidate the relation between plasma tHcy and diabetes mellitus. The result of the present study shows that diabetic patients with the lowest age at onset and with the poorest metabolic control are those most prone to a rapid increase in plasma tHcy concentration. The increment in plasma tHcy concentration in this group of patients may at least partly be explained by a marginal deficiency of blood folate concentrations.
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| 10. |
- Jensen, E, et al.
(författare)
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Plasma homocysteine in 80-year-olds Relationships to medical, psychological and social variables.
- 1998
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Ingår i: Archives of Gerontology and Geriatrics. - 1872-6976. ; 26:3, s. 215-226
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Tidskriftsartikel (refereegranskat)abstract
- Plasma homocysteine concentrations in a group of 80-year-old persons were related to symptoms and signs. Plasma homocysteine concentrations higher than 15 mumol/l were associated with lower total life satisfaction (P<0.01), mood (P<0.05), zest for life (P<0.05), lower scores for reasoning (P<0.05), spatial ability (P<0.05), memory recognition (P<0.05), and subjective health (P<0.01). In an instrument comprising of 30 symptoms, plasma homocysteine concentrations higher than 15 mumol/l were associated with impaired concentration (P<0.05), restlessness (P<0.05), feeling cold (P<0.05), loss of weight (P<0.05), and feeling depressed (P<0.01). The above data indicate that plasma homocysteine values over 15 mumol/l could be relevant markers for clinical intervention.
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