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Biomedical subjects

B Hultberg

Publications and source records attributed to B Hultberg.

At least 91 records · Page 5Linked to original sources

Assessment of renal dysfunction in workers previously exposed to mercury vapour at a chloralkali plant.

Urinary albumin concentration (U-alb) and N-acetyl-beta-D-glucosaminidase (U-NAG) and glomerular basement membrane antibodies (a-GBMs) in serum samples were measured in 77 chloralkali workers previously exposed to mercury (Hg) vapour and 53 age matched referents. The exposure ceased on average 12.3 (range 1-35) years before the study. The mean exposure time was 7.9 (range 1.1-36.2) years. The mean yearly urinary Hg concentration (U-Hg) was 531 nmol/l. The concentrations of the urinary isoenzymes NAG A (U-NAG A) and NAG B (U-NAG B) were determined in 30 highly exposed subjects and 30 referents. No differences in U-alb or U-NAG, U-NAG A, or U-NAG B were found between the groups. Higher concentrations of a-GBMs were found among subjects who stopped exposure a short time before the study, but there was no association between a-GBMs and U-alb. The U-NAG and U-NAG A were negatively correlated with storage time. The results may suggest that microalbuminuria and enzymuria reported in subjects with ongoing exposure to Hg vapour are reversible in most instances.

Acetylglucosaminidase↗

Modification of reticuloendothelial function by muramyl dipeptide-encapsulated liposomes in jaundiced rats treated with biliary decompression.

Rats with 2 weeks of biliary obstruction, with and without 1 week of concomitant biliary decompression relieving the jaundice, were treated with physiologic saline, free muramyl dipeptide (MDP), placebo liposomes, or liposome-encapsulated MDP. Reticuloendothelial system (RES) function was evaluated by blood clearance of intravenously injected 125I-labelled Escherichia coli. The corrected phagocytic index (alpha) after 1 week of biliary decompression returned to normal levels in animals treated with MDP liposomes, whereas RES function was impaired (P < 0.05) in all other jaundiced and biliary-decompressed groups. In the biliary-decompressed, MDP-liposome-treated group, hepatic uptake of radiolabelled bacteria was significantly higher (P < 0.05) and renal entrapment of bacteria was significantly lower (P < 0.05) than in all other jaundiced and biliary-decompressed groups. We conclude that treatment with MDP liposomes improves the otherwise impaired RES function in rats with biliary obstruction and biliary decompression.

Acetylmuramyl-Alanyl-Isoglutamine↗

Plasma homocysteine in renal failure.

Plasma homocysteine in three different groups of patients with chronic renal failure (one group without dialysis, one with CAPD and one with hemodialysis) was increased compared to controls. Another group of patients with slightly reduced renal dysfunction (normal serum creatinine but reduced glomerular filtration rate) did not, however, show increase of plasma homocysteine. The clearance of homocysteine as a percentage of creatinine clearance in the three different groups of patients with chronic renal failure was also significantly increased compared to controls. Thus the clearance of homocysteine was not affected to the same extent as that of creatinine in renal failure. This may be attributed to the fact that, besides the reduced glomerular filtration rate, a depressed tubular uptake of homocysteine may occur in chronic renal failure. We were also able to show that neither in patients with varying renal function nor in controls were there any significant diurnal variation of plasma homocysteine, despite the intake of a protein-rich meal. However, after methionine loading in eight patients with severe chronic renal failure, a slight but significant increase of plasma homocysteine was noted. This indicates a disturbed metabolism with high amounts of homocysteine, which might be mainly attributed to an impaired transulphuration pathway.

Adult↗

The effect of high-dose pyridoxine and folic acid supplementation on serum lipid and plasma homocysteine concentrations in dialysis patients.

Pyridoxine and folic acid supplementation in dialysis patients is a matter of debate. This study was performed to estimate the effects of pharmacologic doses of these vitamins on serum lipid and plasma homocysteine concentrations, which are known to be high in dialysis patients. Both hemodialysis and continuous ambulatory peritoneal dialysis patients were included in the study. Pyridoxine supplementation had a mild but significant cholesterol-lowering effect (7%). Folic acid supplementation significantly lowered plasma homocysteine concentrations by a mean of 30%. There was a strong, inverse correlation between blood folate and plasma homocysteine concentrations. These results indicate that daily supplementation with pyridoxine 300 mg and folic acid 5 mg has a beneficial effect on the cardiovascular risk profile in dialysis patients.

Adult↗

Enzyme immunoassay of beta-hexosaminidase A and B in serum: carrier detection of GM2-gangliosidoses, and equivalence of enzyme activity and enzyme protein reactivity.

beta-Hexosaminidase (Hex; EC 3.2.1.52) isoenzymes A and B were analyzed in sera from a control group of 22 apparently healthy subjects, 13 obligate carriers of Tay-Sachs disease (TSD), 10 obligate carriers of Sandhoff disease (SHD), and 4 affected TSD patients by enzyme immunoassay methods based on enzyme activity. No Hex A activity was detected in the sera of patients with TSD. The activities of Hex A in the obligate carriers of TSD and SHD tended to be lower (nonsignificantly) than in the control group. Hex B activities tended to be higher in TSD patients as well as in carriers of TSD, although the mean activities did not significantly differ from the corresponding mean for the control group. However, Hex B activities were decreased in the carriers of SHD in comparison with the other groups. Sera from 900 postmenopausal women, all of age 55 years, were also analyzed for Hex isoenzymes; the results indicated a carrier frequency of about 1 in 200 for both TSD and SHD. We also compared the enzyme immunoassay method based on enzyme activity with one based on the antigenic (enzyme protein) reactivity alone. Because both methods yielded similar information, we conclude that no significant amounts of inactive enzyme protein are present in the circulation.

Adolescent↗

Homocysteine and other thiols determined in plasma by HPLC and thiol-specific postcolumn derivatization.

We describe a versatile high-performance liquid-chromatographic method for determining homocysteine and other plasma sulfhydryls. Using three different procedures for preparation of plasma, we determined total, free (non-protein-bound), and reduced forms of homocysteine, cysteine, glutathione, cysteinylglycine, and gamma-glutamylcysteine in human plasma. Sample preparation involves disulfide reduction with dithiothreitol and protein precipitation with sulfosalicylic acid. The assay utilizes isocratic reversed-phase ion-pair liquid chromatography at pH 2.4, postcolumn derivatization with 4,4'-dithiodipyridine, and colorimetric detection at 324 nm. The intra-assay precision (CV) of the method for total homocysteine is 1.5%; the interassay precision over 2.5 months is 2.5%. The detection limit for homocysteine is < 50 nmol/L plasma.

Chromatography, High Pressure Liquid↗

Plasma homocysteine in women on oral oestrogen-containing contraceptives and in men with oestrogen-treated prostatic carcinoma.

The mechanism by which oral oestrogen-containing contraceptives in women and oestrogen treatment of prostatic carcinoma in men increases the risk of vascular disease is unclear. These agents decrease serum concentrations of vitamin B12, pyridoxal 5-phosphate, and folate, all of which are essential for the metabolism of the atherogenic amino acid homocysteine. We found serum vitamin B12 concentrations to be lower in 17 women using oral contraceptives (219 +/- 84 pmol l-1) than in 13 age-matched female controls (385 +/- 129, p less than 0.001), but similar values were obtained in the two groups both for fasting plasma homocysteine concentrations (9.1 +/- 2.4 vs 9.2 +/- 3.6 mumol l-1) and for the increase in these concentrations after methionine loading (19.2 +/- 7.5 vs 17.8 +/- 5.2 mumol l-1). In five men with prostatic carcinoma, high-dose oestrogen treatment decreased serum vitamin B12 concentrations by a mean of 30% (p less than 0.05) within 4 weeks, during which fasting plasma homocysteine concentrations decreased (13.8 +/- 4.5 vs 10.5 +/- 2.8 mumol l-1) and response to methionine loading increased (12.4 +/- 3.4 vs 17.3 +/- 5.1 mumol l-1), though the latter changes were non-significant. Our findings do not support the hypothesis that hyperhomocysteinemia explains cardiovascular risk in women using oral oestrogen-containing contraceptives, or in oestrogen-treated men with prostatic carcinoma.

Adolescent↗

Plasma homocysteine before and after methionine loading with regard to age, gender, and menopausal status.

Homocysteine is a probably atherogenic amino acid, the fasting and post-methionine load serum concentrations of which have been reported to be much lower in premenopausal women than in men and postmenopausal women. This difference has been proposed to explain the reduced proneness of premenopausal women to vascular disease. We measured both free and total plasma homocysteine concentrations both fasting and post-methionine load, in 169 healthy subjects. Twelve subjects (7%) had distinctly abnormal plasma homocysteine values. Among the remaining 157 subjects, neither fasting nor post-load values of free or total homocysteine were lower in premenopausal women (n = 46) than in men of similar age (n = 41) or postmenopausal women (n = 37). Fasting but not post-load values were lower in postmenopausal women than in men of similar age (n = 33), and lower among the women as a whole (n = 83) than among the men (n = 74). In men, fasting values increased with age, and paralleled age-related decreases in the concentrations of homocysteine metabolism cofactors (serum vitamin B12, blood folate, and plasma pyridoxal 5-phosphate). Both in men and in women, fasting total plasma homocysteine values were significantly and negatively correlated to serum vitamin B12 and blood folate concentrations. Whether the small differences in plasma homocysteine values between the present men and women may be a contributory factor vis-à-vis their different proneness to vascular disease has yet to be settled.

Adult↗

Elevated urinary beta-hexosaminidase in patients with stroke.

Urinary beta-hexosaminidase is a sensitive indicator of renal damage. The urinary excretion of this enzyme was measured in 31 patients with ischaemic stroke in the acute phase and in 126 patients 21-43 weeks after their stroke. Both immediately and after 21-43 weeks the patients showed a similar and a significantly increased level of urinary beta-hexosaminidase. This indicates the presence of renal injury in the stroke patients, which in turn might reflect a generalized vascular disease.

Biomarkers↗

Rat plasma clearance rate and organ distribution of beta-hexosaminidase isoenzymes from human serum.

beta-Hexosaminidase (EC 3.2.1.30) is markedly increased in human serum in liver disease, chronic alcoholism, and pregnancy. Knowledge of the clearance rate of plasma/serum beta-hexosaminidase is necessary to evaluate this increase. We studied the plasma clearance of beta-hexosaminidase isoenzymes (purified from human serum and placenta) after their infusion into rat circulation. A recently developed enzyme immunoassay method was used to measure the human beta-hexosaminidase isoenzymes; this method relies on both immunoreactivity and enzyme activity, so intact human isoenzymes were measured. In comparison with the placental isoenzymes (t1/2 less than 2 min), the serum forms showed a considerably slower clearance (t1/2 = 2-4 h). However, desialylation of the serum forms resulted in their rapid clearance (t1/2 less than 2 min). The organ localization of the enzyme eliminated from the circulation was investigated 24 h after infusion. Placental and native serum isoenzymes accumulated mainly in the liver and the spleen. Desialylated serum forms were almost exclusively localized to the liver.

Animals↗

Decreased serum homocysteine in pregnancy.

Total serum homocysteine was found to be significantly decreased in the first trimester of pregnancy, became maximal in the second trimester (about 50% compared with non-pregnant women), whereafter the concentration remained stable throughout the remainder of pregnancy. A return to normal concentrations was seen within 2-4 days post partum. Possible reasons for the decrease of serum homocysteine in pregnancy could be haemodilution and increased remethylation of homocysteine due to increased demands for methionine by the foetus.

Adult↗

Elevated urinary excretion of beta-hexosaminidase in smokers.

The excretion of urinary beta-hexosaminidase in 203 apparently healthy males and females correlated significantly with their tobacco consumption (r = 0.26; p less than 0.001). Those who smoked more than 10 g tobacco per day excreted significantly more beta-hexosaminidase in urine than non-smokers, which indicates the presence of a low grade renal injury in smokers.

Creatinine↗

Homocysteine export from erythrocytes and its implication for plasma sampling.

The concentration of free and total homocysteine in plasma increases in time if blood is stored uncentrifuged after sampling. The increase is temperature dependent and the maximal increase in total plasma homocysteine at 37 degrees C was 3.0 mumol.L-1.h-1. Even at 4 degrees C there is a substantial increase, particularly of free plasma homocysteine. Plasma glutathione, cysteinylglycine, and gamma-glutamylcysteine also show an increase in time if whole blood is stored, whereas cysteine decreases. We show that the erythrocytes are responsible for most of the increase in plasma homocysteine and suggest that homocysteine is derived from adenosylmethionine-dependent protein carboxymethylations in the cells. We conclude that strict sampling conditions are necessary when plasma homocysteine and especially its free fraction are assayed.

Adult↗

The association between plasma beta-hexosaminidase and its isoenzyme patterns and retinopathy in type 1 diabetes mellitus.

beta-Hexosaminidase and its isoenzyme patterns were investigated in plasma from patients with Type 1 diabetes mellitus. The patients were divided into three main groups matched for duration of diabetes: (a) proliferative retinopathy (b), progress of retinopathy within a two-year period (c) and with no background retinopathy. When all patients were compared to a reference group, a significant increase of plasma beta-hexosaminidase activity was found. Patients with proliferative retinopathy had significantly increased activity of plasma beta-hexosaminidase compared to the reference group but not compared to the other diabetic patients. The isoenzyme distribution was not different in any of the diabetic subgroups compared to the reference group. It was also shown that various degrees of diabetic nephropathy did not influence total plasma Hex or the isoenzyme pattern.

Adult↗

Influence of hydrolysis on plasma homocysteine determination in healthy subjects and patients with myocardial infarction.

After acid hydrolysis, mean plasma homocysteine concentrations, measured as homocysteine disulphides, of about 1000 and 40 mumol/l have recently been reported in 26 survivors of myocardial infarction and 26 matched control subjects, respectively. This finding contrasts sharply with those more than 50 times lower total homocysteine concentrations found by other research groups in non-hydrolysed plasma from survivors of myocardial infarction. Using the same hydrolysis conditions, we could not detect any homocysteine disulphides in plasma hydrolysates from 9 survivors of myocardial infarction and 10 healthy subjects, who had mean total homocysteine concentrations in non-hydrolysed plasma of 16.9 +/- 6.5 and 15.8 +/- 10.3 mumol/l, respectively. The chromatograms contained several peaks, probably representing peptides, which disappeared with more complete hydrolysis and which might have been misinterpreted as homocysteine disulphides in the reported study. Only after reduction of disulphides and by using a sulphydryl-selective extraction procedure were we able to determine mean homocysteine concentrations in hydrolysed plasma to be 26.2 +/- 7.9 mumol/l in the survivors of myocardial infarction and 24.5 +/- 12.2 mumol/l in the healthy reference subjects. Thus, we could not confirm that survivors of myocardial infarction have homocysteine concentrations that are many times higher than found in healthy subjects.

Adult↗

Serum beta-hexosaminidase isoenzyme: a sensitive marker for alcohol abuse.

Serum beta-hexosaminidase (Hex) isoenzymes analyzed by enzyme immunoassay were investigated in a group of alcoholics (n = 38) hospitalized for detoxication, in another group of alcoholics (n = 22) abstinent between 6 days and 10 years and in a reference group (n = 20). Hex "B" isoenzyme was elevated in all 38 patients hospitalized for detoxication but only 35 of these had total Hex values above the upper limit of the reference group. The Hex A isoenzyme, gamma-glutamyltransferase, and aspartate aminotransferase showed considerable overlap between these patients and the reference group. In the group of 22 abstinent patients only one had an increased level of Hex A, Hex "B," and total Hex, whereas 10 had gamma-glutamyltransferase values above the upper limit of the reference group. It is concluded that Hex "B" is a useful marker for alcohol abuse.

Adult↗

Plasma homocysteine in venous thromboembolism.

Severe hyperhomocysteinemia due to inborn errors of methionine metabolism results in precocious development of arteriosclerosis and predisposition to venous and arterial thromboembolism. Although the findings of several studies have indicated that mild hyperhomocysteinemia is common in occlusive arterial disease, no similar studies have been made on venous thromboembolism. In this study of subjects under 50 years of age, we found no significant differences in the plasma homocysteine concentrations, either in the fasting state or after methionine loading, between 42 patients with venous thromboembolism and 42 healthy controls. Nonetheless, male patients manifested a tendency toward higher homocysteine concentrations than male controls; 6 patients (14%) versus 2 controls (5%) responded abnormally to methionine loading which might indicate heterozygosity for cystathionine synthase deficiency. Thus, further studies on plasma homocysteine in venous thromboembolism are warranted.

Adult↗