1.
2.
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.
3.
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.
4.
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.
5.
6.
Hultberg, Björn, et al.
(författare)
Plasma beta-hexosaminidase isoenzymes A and B exhibit different relations to blood glucose levels in a population of Type 1 diabetic patients
1995
Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 55:8, s. 723-728
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.
7.
Lindblom, Pia, et al.
(författare)
Peripheral effects of PTH are not altered after thyroid surgery in euthyroid patients
2001
Ingår i: Hormone Research. - : S. Karger AG. - 0301-0163. ; 56:3-4, s. 105-109
Tidskriftsartikel (refereegranskat) abstract
Background. We have previously found decreased serum levels of both ionized calcium and 1,25(OH)(2)D and an increase in serum phosphate levels at 1 year after hemithyroidectomy. However, basal and stimulated parathyroid hormone (PTH) secretions were not altered. To investigate whether the observed biochemical changes after unilateral thyroid surgery may be due to a relative end-organ resistance to PTH, we studied the peripheral effects of infused hPTH-(1-34) in 6 patients preoperatively and 3 months after hemithyroidectomy. Methods: Serum levels of TSH, FT4 and FT3 were measured pre- and postoperatively. hPTH-(1-34) was infused at 0.9 IU/kg/h during 6 h. Blood samples for analysis of ionized calcium, intact PTH, phosphate, 25(OH)D, 1,25(OH)(2)D and urinary samples for calcium, phosphate and nephrogenous(n)-cAMP analysis were taken at baseline, when the infusion was discontinued after 6 h and at 24 h. Results: Three months after hemithyroidectomy, serum levels of FT3 were decreased and TSH levels increased. Pre- and postoperative hPTH-(1-34) infusions induced increased serum levels of ionized calcium, 1,25(OH)2D, increased urinary excretion of phosphate and elevated n-cAMP levels. The changes in the studied biochemical variables during the hPTH-(1-34) infusions did not differ between the two study occasions. Conclusion: By using a 6-hour hPTH-(1-34) infusion protocol, we have shown that the peripheral PTH effect is not altered by a slight reduction in thyroid hormone levels at 3 months after hemithyroidectomy.
8.
Lindqvist, Daniel, et al.
(författare)
Salivary cortisol and suicidal behavior-A follow-up study.
2008
Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 33:8, s. 1061-1068
Tidskriftsartikel (refereegranskat) abstract
INTRODUCTION: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA)-axis is a common finding in major depressive disorder. Similar studies on suicide attempters are less abundant, and the results are divergent. The main aim of the present study was to investigate HPA-axis parameters by the time of a suicide attempt and at follow-up in search for associations between HPA-axis function and suicidal behavior. METHODS: Thirty-five suicide attempters and 16 non-suicidal controls were admitted to a psychiatric ward between the years of 1986 and 1992. Corticotrophin-releasing hormone (CRH) in cerebrospinal fluid and urinary cortisol were obtained for the suicide attempters. The patients were followed up approximately 12 years after the index admission. Cortisol was measured in saliva, and additional suicide attempts and current psychiatric symptoms were registered. RESULTS: At follow-up, evening salivary cortisol was lower in suicide attempters compared to controls. Low cortisol levels at follow-up were associated with severe psychiatric symptoms. Among women, repeated suicide attempts were associated with low morning and lunch salivary cortisol, and in this subgroup we also found significant correlations between salivary cortisol at follow-up, and CRH as well as urinary cortisol at index. CONCLUSION: We found evidence for an association between low HPA-axis activity and suicidal behavior. This could be due to long-lasting and severe psychiatric morbidity, which in turn has exhausted the HPA-axis of these patients. The potential role of hypocortisolism should be given more attention in studies on suicidal patients.
9.
10.
Marques, Paul, et al.
(författare)
Detection of Phosphatidylethanol (PEth) in the Blood of Drivers in an Alcohol Ignition Interlock Program
2011
Ingår i: Traffic Injury Prevention. - : Informa UK Limited. - 1538-9588 .- 1538-957X. ; 12:2, s. 136-141
Tidskriftsartikel (refereegranskat) abstract
Objective: The rate of failed interlock blood alcohol content (BAC) tests is a strong predictor of recidivism post-interlock and a partial proxy for alcohol use. Alcohol biomarkers measured at the start of an interlock program are known to correlate well with rates of failed BAC tests over months of interlock use. This study evaluates 2 methods of measuring low blood levels of the biomarker phosphatidylethanol (PEth). PEth is a 100 percent alcohol-specific biomarker and strongly intercorrelated with several independent indicators of drinking driving risk, including 8 other biomarkers, 3 psychometric assessments, and the rate of failed interlock BAC tests during many months of interlock use. Does a more sensitive method of measuring PEth at program entry detect drinking even among those who subsequently log no failed interlock tests? Methods: In a sample of 281 driver blood samples, PEth was measured by both high-performance liquid chromatography (HPLC) and liquid chromatography tandem mass spectrometry (LCMSMS) in order to compare sensitivity and accuracy. The average rate of failed interlock BAC tests was the criterion measure for marker sensitivity. LCMSMS, calibrated to detect low levels of drinking as a possible measure of abstinence violation, was judged relative to the standard HPLC assay for PEth measured up to 4 mol/L. Results: The 2 methods showed a good quantitative relationship (r2 .86). LCMSMS detected positive PEth levels in samples that were below the limit of detection of the HPLC method. PEth measured by LCMSMS was positive for a higher proportion of driving under the influence (DUI) offenders who logged zero failed interlock BAC tests than were detected by HPLC. Conclusion: Although HPLC is the widely used standard for measuring PEth in clinical alcoholism samples, the LCMSMS method, when calibrated to detect trace amounts of the major component of PEth, can detect abstinence levels of alcohol near zero intake and still correlate strongly with other indicators related to alcohol use and road safety.
