| 1. |
- Agardh, Carl-David, et al.
(författare)
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Lack of association between plasma homocysteine levels and microangiopathy in type 1 diabetes mellitus
- 1994
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 54:8, s. 637-641
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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.
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| 2. |
- 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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| 3. |
- Ahola, T, et al.
(författare)
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Thiol metabolism in preterm infants during the first week of life
- 2004
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 64:7, s. 649-658
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Tidskriftsartikel (refereegranskat)abstract
- Background: Oxidative stress is implicated in the pathogenesis of several complications of prematurity. The glutathione cycle is one of the most important intracellular antioxidant systems. The synthesis of glutathione may not be adequate in preterm neonates because of the low levels of cysteine available. The aim of this study was to evaluate cysteine and glutathione metabolism during the first week of life in preterm infants. Methods: Plasma and erythrocyte thiol concentrations were measured in 78 preterm infants with a birthweight of 500 1500 g, and erythrocyte glutamate-cysteine ligase (GCL), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferases (GST) and glucose 6-phosphatedehydrogenase (G6PDH) in 26 infants with a birthweight of 1000 - 1500 g. Results: The mean (SD) plasma glutathione concentration increased from day 0 to day 1 (14.9 (7.1) vs. 27.7 (11.9) mumol/L, p<0.001), and then decreased. The plasma cysteine concentration changed in the opposite direction ( 172 (59) vs. 129 (42) μmol/L, p<0.01). In infants with respiratory distress syndrome (RDS) the mean plasma glutathione concentration, but not cysteine, was lower on day 0 compared with infants without RDS (11.7 (5.2) vs. 21.4 (5.6) mumol/L, p<0.01). Erythrocyte glutathione concentration decreased during the first week of life, whereas erythrocyte cysteine concentration increased significantly from day 3 to day 7 (p<0.01). Erythrocyte cysteine and glutathione concentrations had a positive correlation. The GCL and GR activities did not change, but GST and G6PDH activities decreased during the first week (p<0.01). GPx activity decreased until day 3 (p<0.01) and was higher on day 0 and day 1 in infants with RDS. Conclusions: Very low birthweight infants have an initial increase in plasma glutathione and initial decrease in plasma cysteine level during the first week of life, and also a positive correlation between erythrocyte cysteine and glutathione levels.
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| 4. |
- Almquist, Martin, et al.
(författare)
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Reproductive history, lifestyle factors and season as determinants for serum calcium concentrations in women.
- 2008
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 68, s. 777-785
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Serum calcium concentrations have been associated with the risk of malignant disease, especially breast cancer. Thus, determinants of serum calcium concentrations, with special regard to risk factors of breast cancer, are of great interest. Material and methods. Previous studies have either been small or they have not focused on reproductive factors. The present study examined serum calcium concentrations in relation to reproductive history, selected lifestyle factors and screening season in a large population-based cohort study comprising 8,114 women. ANOVA followed by the Bonferroni t-test were used for comparison of means, and logistic regression and multiple regression analysis were used to test associations. Results. Serum calcium concentrations were lower in hormone replacement therapy users versus non-users (2.321 mmol/L versus 2.364; p<0.001) and in users of oral contraceptives versus non-users (2.304 versus 2.348; p<0.001). They were higher in peri-/postmenopausal versus premenopausal women (2.357 versus 2.319; p<0.001). Overweight and obese women had higher mean calcium concentrations (2.350 and 2.355) than women with body mass index between 20 and 25 (2.342; p<0.001). Serum calcium concentrations were higher in spring and autumn than in winter (2.352 and 2.353 versus 2.343; p = 0.002). Both younger (40-45 years) (2.334; p = 0.001) and older age groups (>55 years) (2.363; p<0.001) had higher mean calcium concentrations compared to those of women aged 45-50 years (2.320), even when adjusting for menopausal status, suggesting that age has an independent influence on calcium concentrations. Conclusions. It is concluded that reproductive factors such as menopausal status, use of oral contraceptives or hormone-replacement therapy, and age, BMI and season are associated with serum calcium concentrations.
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| 5. |
- Almqvist, Erik G., et al.
(författare)
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Factors influencing insulin sensitivity in patients with mild primary hyperparathyroidism before and after parathyroidectomy
- 2012
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 72:2, s. 92-99
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. Primary hyperparathyroidism (PHPT) is associated with cardiovascular disease. The aims of this study were to investigate lipid and glucose metabolism in mild PHPT, and to identify whether insulin sensitivity correlates with circulating levels of adiponectin, SHBG, and osteocalcin before and after parathyroidectomy (PTX). Materials and methods. Forty-five patients with PHPT were examined before and 1 year after PTX. Circulating levels of triglycerides, total cholesterol, HDL-cholesterol, insulin, glucose, adiponectin, SHBG, osteocalcin, and erythropoietin were measured. Results. At baseline, the mean serum levels of total cholesterol, LDL-cholesterol and triglycerides were above the upper reference limit or in the upper normal range, and insulin sensitivity was reduced as assessed using the HOMA index. One year after parathyroidectomy, serum lipids as well as HOMA index and erythropoietin were unchanged while adiponectin had increased (p < 0.05), and SHBG and osteocalcin had decreased (p < 0.05 and p < 0.0001, respectively). HOMA index correlated negatively with circulating levels of adiponectin, SHBG and osteocalcin. In multiple regression analysis SHBG was the most important predictor of insulin sensitivity, both pre- and postoperatively. Conclusion. Untreated mild PHPT is associated with a moderate derangement of lipid and glucose metabolism. As previously shown in population-based cohorts, insulin sensitivity is positively associated with circulating concentrations of adiponectin, SHBG and osteocalcin. One year after PTX, the mean level of adiponectin was increased, but the levels of SHBG and osteocalcin had decreased and the levels of serum lipids and the insulin sensitivity remained unchanged as compared with baseline.
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| 6. |
- Almqvist, E G, et al.
(författare)
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Hypothalamic-pituitary-adrenal response to different tests in type 1 diabetes mellitus
- 2001
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 61:7, s. 557-565
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether different tests of the adrenocorticotropic hormone (ACTH) reserve are influenced by diabetic state and metabolic control in newly diagnosed type 1 diabetic patients. DESIGN AND METHODS: We evaluated the ACTH reserve in 10 patients with uncomplicated type 1 diabetes during periods of poor and improved metabolic control and in 10 healthy subjects. The ACTH-cortisol secretion was assessed by a diurnal profile, an intravenous corticotropin-releasing hormone (CRH) test and an insulin tolerance test (ITT). RESULTS: The diurnal profiles were similar in all groups. CRH resulted in a diminished ACTH response during poor compared with improved metabolic control (mean+/-SD) (AUC 4950+/-4227 vs. 5847+/-3788 ng/L min, p<0.05). The response in the diabetic patients during improved metabolic control was of the same magnitude as in the control subjects (5934+/-1778 ng/L x min). ITT elicited a similar ACTH and cortisol response in the diabetic patients during poor and improved metabolic control as in the healthy control subjects. CONCLUSIONS: The ITT was uninfluenced by diabetic state and metabolic control and should therefore be considered the method of choice in evaluation of the ACTH reserve in patients with type 1 diabetes.
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| 7. |
- Almqvist, Erik G., et al.
(författare)
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Increased markers of inflammation and endothelial dysfunction in patients with mild primary hyperparathyroidism
- 2011
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 71:2, s. 139-144
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The association between primary hyperparathyroidism (PHPT) and cardiovascular disease is incompletely understood. The aims of this study were to evaluate how cardiac function and markers of inflammation and endothelial dysfunction correlate in patients with mild PHPT, and how these markers are influenced by surgical cure of the parathyroid disease (PTX). Material and methods: Forty-five patients with PHPT were examined before and 1 year after PTX. Serum/plasma concentrations of calcium, PTH, highly sensitive C-reactive protein (CRP), interleukin-6 (IL-6), vascular adhesion molecule-1 (VCAM1), E-selectin, and NT-proBNP were measured as well as erythrocyte sedimentation rate (ESR) and creatinine clearance. Cardiac function was evaluated by equilibrium radionuclide angiography. Results: The baseline serum level of IL-6 correlated negatively with baseline parameters of cardiac function (exercise capacity, p < 0.001, left ventricular ejection fraction at exercise, p < 0.01). The mean serum concentrations of IL-6 and CRP and the ESR had increased 1 year after PTX (p < 0.001, p < 0.01, and p < 0.001, respectively) in parallel with a decrease in cardiac function and an increase in circulating NT-proBNP. The mean serum level of VCAM1 was above the upper normal range at baseline and had not changed significantly 1 year after PTX. Conclusion: Patients with mild PHPT and normal renal function displayed signs of subclinical inflammation and endothelial dysfunction. One year after PTX, the inflammatory markers were increased in parallel with a subclinical decrease in cardiac function. Further studies are warranted to clarify the natural course and clinical implications of these changes.
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| 8. |
- Arnadottir, Margret, et al.
(författare)
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Effects of short-term treatment with corticotropin on the serum apolipoprotein pattern
- 2001
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 61:4, s. 301-306
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with adrenocorticotrophic hormone (ACTH) has a well-documented cholesterol-lowering effect. Increased uptake of low-density lipoprotein (LDL) by HepG2 cells in response to incubation with ACTH has been demonstrated but the precise cholesterol-lowering mechanism has resisted elucidation. Since apolipoproteins are important determinants of lipoprotein metabolism, we sought to extend the knowledge of the effect of ACTH treatment on the serum apolipoprotein (apo) pattern. Twelve healthy individuals and 14 dyslipoproteinemic hemodialysis patients were recruited. The two groups responded similarly to ACTH1-24 at the dose of 1 mg daily for four days. In accordance with previous results, serum concentrations of total cholesterol decreased by 18% and 17%, LDL cholesterol by 25% and 30%, and apo B by 20% and 19%, respectively, while there were no significant changes in the serum concentrations of triglycerides, high-density lipoprotein cholesterol and apo AI. Novel findings were that the serum concentrations of total apo E increased by 48% and 31%, and apo B-associated apo E by 69% and 46%, respectively. Moreover, in the healthy individuals, the serum concentrations of apo CIII did not change in response to ACTH, whereas in the hemodialysis patients, those of apo CIII not associated with apo B increased significantly by 44%. Since apo E binds strongly to the LDL receptor, the present results suggest that the cholesterol-lowering effect of ACTH may be mediated by facilitated hepatic uptake of apo E-enriched apo B-containing lipoproteins. Thus, the findings stimulate further research.
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| 9. |
- 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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| 10. |
- Axelsson, L., et al.
(författare)
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Studies of the release and turnover of a human neutrophil lipocalin
- 1995
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 55:7, s. 577-588
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Tidskriftsartikel (refereegranskat)abstract
- A 24-kDa protein was purified from human neutrophil extracts and shown to be the newly discovered neutrophil gelatinase-associated lipocalin (NGAL), based on structural and immunochemical data. A specific enzyme-linked immunosorbent assay (ELISA) was developed for the determination of NGAL in human plasma and tissue fluids. Normal human plasma contains 72 μg 1-1 of NGAL (range 40-109 μg 1-1) in two main forms, monomer and dimer. 35S-methionine metabolic studies of human neutrophils showed that granulocyte macrophagecolony-stimulating factor (GMCSF) stimulated significant synthesis and secretion of NGAL in a dose- and time-dependent fashion. NGAL was rapidly released as monomer and dimer on incubation of heparinized whole blood with opsonized yeast, reaching a plateau corresponding to about 35% of total cell content after 30 min. Following intravenous injection of 125-iodine labelled NGAL there was a more rapid initial clearance of the monomeric than of the dimeric form; t1/2 10 min vs. 20 min. During the second phase the two forms cleared at similar rates. Severe acute peritonitis was accompanied by a 10-fold increase in NGAL plasma levels and the NGAL level in peritoneal exudates, which reached about 40 mg 1-1. There was a good linear correlation between the concentrations of NGAL, leucocyte elastase and NP4 (neutrophil proteinase 4 = P3).
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