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Biomedical subjects

F Tatzber

Publications and source records attributed to F Tatzber.

36 records · Page 2Linked to original sources

Enhanced plasma level of lipid peroxidation in Iranians could be improved by antioxidants supplementation.

OBJECTIVE: To study the influence of supplementation with antioxidants on factors, which might increase the risk of coronary heart disease (CHD) in Iranians. DESIGN: Twenty-one male volunteers enter the prospective, single-blind, randomized study. SETTING: The supplementation was conducted at the Cardiovascular Center, University of Tehran, the biochemical analysis were carried out in the University of Graz. SUBJECTS: Twenty-one male medical students were recruited by advertisement. Five subjects were dropped out due to lack of the compliance. METHODS: One group of Iranians received 30 mg/d beta-carotene and placebo for alpha-tocopherol; the other received beta-carotene plus 400 IU alpha-tocopherol for ten weeks. Concentrations of antioxidants in plasma and low density lipoproteins (LDL), plasma lipid profile, autoantibody against oxidized LDL (oLAb) and malondialdehyde (MDA) concentrations in plasma were measured. Oxidative resistance of LDL was estimated using conjugated diene assay. RESULTS: Iranians had a significantly lower plasma levels of total cholesterol (P < 0.002), LDL-cholesterol (P < 0.01) and high density lipoprotein-cholesterol (P < 0.002), compared to healthy Austrian subjects (n = 13). Although the baseline concentrations of alpha-tocopherol and beta-carotene were comparable with Austrians, lycopene, canthaxanthin and lutein were significantly higher in Iranians (P < 0.03-0.001). In vitro oxidative resistance of LDL, measured as lag-time, was slightly higher (P < 0.01) in Iranians comparing with Austrians. Plasma MDA and oLAb concentrations were significantly higher in Iranians (P < 0.001). Both dietary supplementations reduced plasma MDA concentrations (P < 0.001-0.001). A key finding was that a supplement combined with alpha-tocopherol caused also a significant increase of oLAb concentration (P > 0.01) as well as the significant increase of lag-time (P > 0.005). CONCLUSIONS: This study shows that high plasma MDA level of Iranians can be decreased by beta-carotene supplementation with or without alpha-tocopherol. However, alpha-tocopherol is a more powerful antioxidant, which can increase the resistance of LDL to oxidation, reduce the MDA concentrations in plasma and increase autoantibodies to oLDL.

Adult↗

Analysis of the in vitro secretory activity of human pituitary adenomas: modification of corticotropin release from adenoma tissue explant cultures by addition of a human plasma ultrafiltrate bioactive fraction.

The lack of control of tumour behaviour is manifested in different ways, depending primarily on the type of tumour. This results in numerous problems of tumour diagnosis and therapy. In the case of "benign" tumours, like pituitary adenomas, in vitro studies are often used for evaluation of the tumour. The use of tissue explant cultures of human pituitary adenomas and the comparison of the feature of cultured tumours with their behaviour in vivo showed that corticotropin is released not only from the tumours associated with Cushing's disease, but also from clinically non-functioning tumours. Hence, it was supposed that the release of corticotropin in vivo from non-secreting tumours is probably under the influence of certain neuroendocrine and/or systemic humoral factors. To test this possibility, samples of 22 tumours were cultured in plain culture medium or in the presence of the "human plasma ultrafiltrate bioactive fraction" (tentatively termed as TBP) prepared by anion-exchange chromatography. In the presence of TBP the release of corticotropin was strongly inhibited in adenomas showing relatively high spontaneous secreting activity in vitro (> 200 ng/l in 24 hours), while immunohistochemistry of these tumours indicated accumulation of corticotropin inside the cells. In contrast, TBP stimulated corticotropin release from tumours that showed relatively low basic corticotropin release (< 200 ng/l in 24 hours), with no obvious change in cellular corticotropin immunoreactivity. Such a dual activity of TBP was not observed for 8 samples of adenomas cultured in the presence of surrounding pituitary tissue, probably because TBP did not affect corticotropin secretion by the normal pituitary cells (as indicated by immunohistochemistry). From these results, it appears that TBP could be one of the humoral factors involved in the regulation of corticotropin release from pituitary adenoma tissue. Its possible involvement in the regulation of corticotropin release from normal pituitary tissue, however, is uncertain.

Adenoma↗

Intake of mercury from fish, lipid peroxidation, and the risk of myocardial infarction and coronary, cardiovascular, and any death in eastern Finnish men.

BACKGROUND: Even though previous studies have suggested an association between high fish intake and reduced coronary heart disease (CHD) mortality, men in Eastern Finland, who have a high fish intake, have an exceptionally high CHD mortality. We hypothesized that this paradox could be in part explained by high mercury content in fish. METHODS AND RESULTS: We studied the relation of the dietary intake of fish and mercury, as well as hair content and urinary excretion of mercury, to the risk of acute myocardial infarction (AMI) and death from CHD, cardiovascular disease (CVD), and any cause in 1833 men aged 42 to 60 years who were free of clinical CHD, stroke, claudication, and cancer. Of these, 73 experienced an AMI in 2 to 7 years. Of the 78 decreased men, 18 died of CHD and 24 died of CVD. Men who had consumed local nonfatty fish species had elevated hair mercury contents. In Cox models with the major cardiovascular risk factors as covariates, dietary intakes of fish and mercury were associated with significantly increased risk of AMI and death from CHD, CVD, and any death. Men in the highest tertile (> or = 2.0 micrograms/g) of hair mercury content had a 2.0-fold (95% confidence interval, 1.2 to 3.1; P = .005) age- and CHD-adjusted risk of AMI and a 2.9-fold (95% CI, 1.2 to 6.6; P = .014) adjusted risk of cardiovascular death compared with those with a lower hair mercury content. In a nested case-control subsample, the 24-hour urinary mercury excretion had a significant (P = .042) independent association with the risk of AMI. Both the hair and urinary mercury associated significantly with titers of immune complexes containing oxidized LDL. CONCLUSIONS: These data suggest that a high intake of mercury from nonfatty freshwater fish and the consequent accumulation of mercury in the body are associated with an excess risk of AMI as well as death from CHD, CVD, and any cause in Eastern Finnish men and this increased risk may be due to the promotion of lipid peroxidation by mercury.

Adult↗

Transient reduction of autoantibodies against oxidized LDL in patients with acute myocardial infarction.

Fifteen consecutive patients (mean age 66 +/- 14, range 31-82) with an acute myocardial infarction (MI) suitable for thrombolytic therapy were included in this study. Autoantibodies against oxidized low-density lipoprotein (LDL) were determined by enzyme-linked immunosorbent assay (ELISA). Patients (n = 10) with marked elevation of the MB isoenzyme of creatinine kinase (CK-MB)-mass had significant decreases of oLDL-Ab during the acute phase, with a minimum after 8 h following the onset of thrombolytic therapy (within-group significance: p < .001; between groups: p = .01). Patients (n = 5) with CK-MB-mass values less than 70 ng/ml did not show this phenomenon. Furthermore, significant correlations existed between CK-MB-mass and oLDL-Ab after 6 and 8 h (n = 15; r = .72; p = .003) and the time of the highest CK-MB-mass values (after 12 h) and the time of the maximal decrease of oLDL-Ab (after 8 h) (r = .74; p = .003). Our observations provide further evidence for the release of free radicals and for increased lipid peroxidation during reperfusion after prolonged ischemia. The decrease of oLDL-Ab appears to be a marker for the severity of MI.

Adult↗

Autoantibodies to oxidized low density lipoproteins in restenosis following coronary angioplasty.

Oxidized low density lipoproteins (oLDL) play an important role in the pathogenesis of atherosclerosis. Recently, elevated oLDL autoantibodies in serum were shown in patients with severe peripheral atherosclerosis. To evaluate their role in restenosis after percutaneous transluminal coronary angioplasty (PTCA), oLDL autoantibodies were determined in a randomly selected series of 48 males following successful PTCA. Follow-up angiography as well as blood sampling were done 12 months after PTCA; restenosis was defined as > or = 50% reduction in diameter of the coronary artery. Twenty-six patients (mean age: 56 years) showed restenosis (Restenosis Group), whereas 22 (mean age: 53 years) had open vessels (Patent Vessel Group). Both groups did not differ in age, past medical history, fibrinogen and lipid profile as well as in initial angiographic findings. Oxidized LDL autoantibodies were 13 +/- 21 U in the Restenosis Group and 6 +/- 4 U in the Patent Vessel Group, showing no significant difference. Six of 26 patients in the Restenosis Group and 3 of 22 in the Patent Vessel Group (NS) had elevated oLDL autoantibody levels (> or = 10 U). Thus, although there is a trend to elevated oLDL autoantibodies in males with restenosis of coronary arteries, oLDL cannot serve as a strong marker for stenosis following PTCA.

Adult↗

A multivitamin infusion prevents lipid peroxidation and improves transplantation performance.

The objective of this study was to test the hypothesis that ischemia reperfusion damage in kidney transplantation is associated with lipid peroxidation and that inhibition of lipid peroxidation by antioxidants improves the function of the transplanted kidney. Lipid peroxidation was assessed by measuring the plasma malonaldehyde content (as thiobarbituric acid reaction product) with high-performance liquid chromatography. Kidney function was assessed by plasma creatinine and creatinine clearance. Thirty patients of an ongoing series were randomly selected into two groups, with 14 controls and 16 patients in the antioxidant therapy group. Therapy consisted of two ampoules of Omnibionta (which contains vitamins C, E, A and B complex) diluted in 500 ml physiological sodium chloride, which was infused intravenously prior to reperfusion onset. No significant differences existed for the age of the patients in the control (43.00 +/- 9.86 years) and the therapy group (41.56 +/- 14.14 years) nor in the kidney preservation time, which was 24.12 +/- 8.73 and 18.43 +/- 9.97 hours in the control and therapy group, respectively. The controls showed a transient increase of plasma lipid peroxides as measured by malonaldehyde with a peak one hour after onset of reperfusion. Compared to the baseline value of 0.74 +/- 0.26 (mean +/- SD) the one hour malonaldehyde value increased to 1.46 +/- 0.22 nmol/ml (P < 0.001). In the therapy group the plasma malonaldehyde level did not increase, but slightly decreased by about 20% compared to the baseline value. The difference of plasma malonaldehyde between the two groups one hour after reperfusion onset was highly significant (P > 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Presence of foam cells containing oxidised low density lipoprotein in the synovial membrane from patients with rheumatoid arthritis.

OBJECTIVE: Increased concentrations of lipid peroxidation products have been described in the serum and synovial fluid from patients with rheumatoid arthritis. A large proportion of the unsaturated lipids in human extracellular fluids is a component of low density lipoprotein (LDL). The oxidative modification of LDL, and its subsequent uptake by macrophages, has been implicated in the pathogenesis of atherosclerosis, but not of rheumatoid arthritis. This study aimed to assess whether oxidatively modified LDL was present in the rheumatoid synovium. METHODS: A polyclonal antiserum raised in rabbits against oxidised LDL (o-LDL) was used to perform an immunohistochemical study of a series of synovial biopsy specimens from patients with rheumatoid arthritis. RESULTS: Collections of positively stained macrophages, arranged in a linear fashion and with the morphological characteristics of foam cells--that is, 'fatty streaks', were identified around blood vessels within the intimal connective tissue. In addition, scattered, positively stained foam cells were present in association with deposits of fibrin. These staining patterns were absent from control synovial membranes (traumatic knee injuries). CONCLUSIONS: The findings in all rheumatoid patients studied suggest that atherosclerosis and rheumatoid arthritis have analogous pathogenetic features.

Arthritis, Rheumatoid↗

Inhibition of LDL oxidation by antioxidants.

Low density lipoprotein (LDL) consists of about 3000 fatty acids (50% polyunsaturated) and a single molecule apolipoprotein B (500 kDa). The endogenous antioxidants of LDL consist mainly of tocopherols and few carotenoids, which protect the PUFAS against oxidation. That native LDL contains traces of oxidation products has not been proved yet. Oxidatively modified LDL (oLDL) exhibits cytotoxic and chemotactic activities, furthermore it leads to foam cell formation, a critical step in atherogenesis. The oxidation of LDL is a free radical process and leads to various aldehydic products. The oxidation of LDL is initiated by cells as well as by transition metals like Cu2+. In both cases the oxidation goes through three consecutive phases. The lag-phase is characterized by minimal degradation of PUFAs but a loss of the antioxidants. Thereafter the PUFAs are oxidized to lipid hydroperoxides, which are only intermediates (propagation-phase). These intermediates will decompose to aldehydic products, accompanied by several additional changes in the LDL particle (decomposition-phase). For increased macrophage uptake oLDL must reach the late decomposition-phase; the presence of lipid hydroperoxides in LDL is not sufficient. It is suggested that binding of aldehydes to free amino groups of Apo B is the reason for macrophage uptake. This is supported by the finding that antibodies against aldehyde-modified LDL are able to recognize oxidized LDL in atherosclerotic lesions. Antioxidants like alpha-tocopherol are able to protect LDL against oxidation. The duration of the lag-phase shows a linear relationship with the content of alpha-tocopherol in LDL. Yet the efficiency of alpha-tocopherol to protect LDL shows strong individual variation.

Animals↗

Human plasma lipid peroxide levels show a strong transient increase after successful revascularization operations.

This study was performed to evaluate the hypothesis that oxygen radicals/lipid peroxidation are involved in reperfusion injury in humans. The study included 37 patients, who underwent surgical revascularization operations for kidney transplantation (9 subjects) or limb salvage (28 subjects). Peripheral venous blood samples were taken 30 min before starting reperfusion (baseline) and 1, 2, 3, 4, and occasionally 6 to 18 h after revascularization. The amount of plasma malonaldehyde formed in the reaction with thiobarbituric acid (MDA-TBA) was determined by high-performance liquid chromatography (HPLC). The baseline MDA-TBA values of the patients were very close to the value determined for 20 age-matched healthy subjects (i.e. mean +/- SD 0.689 +/- 0.294 nmol/mL plasma [range 0.2 to 1.37] vs. 0.700 +/- 0.209 nmol/mL plasma [range 0.385 to 1.29]). All patients responded to successful revascularization with significant increase of the plasma MDA-TBA within about 1 h after onset of reperfusion. Thereafter the values decreased nearly to the preoperative state. The mean increase of MDA-TBA was 107% in kidney transplantation and 54% in limb revascularization. In a few patients with severe arteriosclerosis, revascularization was not optimal and no increase in the MDA-TBA value occurred. The results of this study indicate that therapeutic intervention to prevent lipid-peroxidation-mediated reperfusion injury is confined to a rather narrow time window and must be undertaken either prior to or immediately after revascularization.

Aged↗

Biologic and cytogenetic characterization of three human medullary thyroid carcinomas in culture.

Neuroendocrine features and cytogenetic abnormalities of one continuous cell line (MTC-SK) and two long-term cultures (GER, STAH) derived from three sporadic cases of human medullary thyroid carcinomas (MTCs) were studied. Specific neuroendocrine markers (NSE, chromogranins, calcitonin, calcitonin gene-related peptide) were identified by electron microscopy and immunocytochemistry. In situ hybridochemistry and Northern blot analysis confirmed endocrine activity. Cytogenetic studies of the cell line MTC-SK revealed three consistent marker chromosomes, t(3;10), 11p+, and 22p+. Cells of long-term cultures GER and STAH exhibited a consistent translocation t(2;18), a trisomy 7, and two consistent marker chromosomes der3 and 5p+, respectively. Recently, we have isolated 12 stable clones of this MTC-SK cell line, which showed two different growth patterns. Quantitative measurement of mitotic activity flow cytometry and semiquantitative analysis of AgNOR-, Ki67-, and Cyclin/PCNA-(immuno)reactivity showed different DNA composition and duplication rates, indicating at least two subpopulations. Some of our clones developed a new consistent marker (i.e., an unbalanced translocation between mar11p+ and 1q). However, no correlations between chromosome findings, growth rate, and neuroendocrine markers were observed.

Carcinoma↗

Elevated serum neopterin levels in atherosclerosis.

Plasma levels of neopterin were determined in patients with different clinical stages of atherosclerosis. Non-hospitalized patients with atherosclerosis had serum and plasma neopterin levels within the normal range of the assay (6 +/- 2 nM). These values were not significantly different from those reported for healthy blood donors (5 +/- 2 nM). In contrast, about 50% (29 out of 61) of hospitalized patients undergoing conservative or surgical therapy had neopterin plasma levels, which exceeded the normal range (greater than 10 nM) up to 10-fold. The two groups differ on a significance level of P less than 0.01. For further evaluation hospitalized patients were subgrouped according to neopterin levels. In the subgroup with elevated neopterin levels patients with higher Frederickson types of atherosclerosis were overrepresented compared to patients with normal neopterin levels. Type 4 differed significantly from patients without pathological changes of lipoprotein (P less than 0.05). Only 3 patients suffered from minimal skin necrosis, two of them had elevated neopterin levels. Significantly more patients with peripheral artery occlusions had elevated neopterin levels than patients with occlusions of central arteries (P less than 0.05). All other criteria used for comparison (sex, age, smoking, antioxidant status, diabetes, hypertension, adipositas, hyperuricemia) did not vary significantly in both subgroups. These data indicate that neopterin plasma levels might be a valuable parameter in activity staging and therapeutic follow up of atherosclerotic patients. Additionally, an involvement of the nonspecific immune system in atherogenesis is suggested by the increased plasma neopterin concentrations.

Aged↗

Pathogenesis of Herpes simplex virus infections in guinea pigs.

The pathogenesis of herpes simplex virus types 1 and 2 has been studied in guinea pigs after inoculation by various routes (subcutaneous and intradermal infection in footpads and vaginal infection). Clinical observations as well as virus isolation studies are reported. Herpes simplex virus type 2 infection by all three routes of inoculation led to acute primary and recurrent lesions. Virus persisted in the nervous system, particularly in sensory ganglia, and locally at the site of inoculation. Herpes simplex virus type 1 infection induced no or very mild primary symptoms. Recurrent lesions were only observed after intradermal inoculation. Invasion of the nervous system and consequent establishment of latent ganglionic infection was less efficient than after herpes simplex virus type 2 infection. Peripheral persistence was, however, equally common.

Animals↗