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Biomedical subjects

H Sinzinger

Publications and source records attributed to H Sinzinger.

At least 55 records · Page 3Linked to original sources
PubMed2001

Prostaglandins and lipid modification.

Postaglandins(PG) and low-density lipoproteins (LDL) both are playing a key role in atherogenesis. Their interaction at the local vascular level is of central relevance in plaque formation and progression. Details of these complex actions however, still need to be elucidated. Lipoproteins are influencing the PG-production of arterial wall cells and platelets, while PGs in turn have been shown to regulate lipoprotein receptor binding and entry into the arterial wall. Modification of LDL severely influences arterial wall trapping and foam cell formation. During LDL-modification, isoprostanes, a new family of compounds generated by free radical catalysed action, independent of cyclooxygenase, are formed. 8-epi PGF(2alpha) the most well known member exerts a great variety of proatherogenic actions, among them vasoconstriction and platelet activation; it also serves as a mitogen and stimulator of endothelin release. The influence of various eicosanoids on lipoprotein modification, however, has not been assessed yet.

Arteriosclerosis↗
PubMed2000

Quitting cigarette smoking results in a fast improvement of in vivo oxidation injury (determined via plasma, serum and urinary isoprostane).

Isoprostanes (IP) have been identified as reliable markers of in vivo oxidation injury. Recently, in vascular tissue and blood as well as urine of cigarette smokers, increased IP values have been discovered. We examined 47 adults (26 males, 21 females; aged 30-66 years), admitted to a cardiovascular unit on an outpatient basis, with various risk factors but without any sign of manifestation of atherosclerosis. Refraining from cigarette smoking for a few days resulted in a significant drop of plasma, serum, and urinary 8-epi-PGF(2alpha). Thereafter, a further continuous decrease was monitored, reaching a steady state after about 4 weeks after quitting cigarette smoking. Prevalues of 8-epi-PGF(2alpha) were higher, depending on the type and number of risk factors; the decrease after quitting, however, was comparable. These results indicate that exsmokers may rapidly recover from their enhanced in vivo oxidation.

Adult↗
PubMed2000

Troglitazone-binding to LDL and its glycated modifications: its role in cell-catalysed and Cu-mediated LDL-oxidation.

Troglitazone (T), an anti-diabetic drug improving insulin resistance, was studied as to its inhibition of copper ion-catalysed oxidation of native, glycated and glycoxidated low-density lipoprotein (LDL). A dose-dependent inhibition was noted in the concentration range 40-160 microg/ml. An almost complete inhibition of oxidation (2-8 h), as monitored by the formation of thiobarbituric acid-reactive substances, was observed for both native and glycated LDL at a concentration of 160 microg/ml T, while the maximal inhibition for glycoxidated LDL amounted only to 60% at this concentration of the drug. This is reflected by differences in the affinity of the drug for the different types of LDL modification: While the binding of T both to native or glycated LDL increased linearly with increasing T concentration and was not saturable in the concentration range tested (0-160 microg/ml), binding of the drug to glycoxidated LDL was already nearly saturated at 10 microg/ml. The nearly complete inhibitory action of T towards oxidation of native and glycated LDL was lost, however, upon increasing the total oxidation time to 24 h. In human umbilical vein endothelial cell-mediated oxidation of LDL, T at a concentration of 20 microg/ml significantly reduced formation of oxidation-dependent fluorescent chromophores and liberation of 8-epi-PGF2alpha. In contrast, generation of thiobarbituric acid-reactive substances was not significantly inhibited. As opposed to copper-mediated LDL-oxidation, different binding of T to LDL-modifications does not govern inhibition of human umbilical vein endothelial cell-mediated LDL-oxidation.

Adult↗
PubMed2000

Homocysteine--relevant for atherogenesis?

Numerous studies report strong associations between hyperhomocysteinemia and premature atherosclerotic vascular disease. Causes of hyperhomocysteinemia are hereditary heterozygous or, in very rare cases, homozygous defects, and quite frequently a lack of the coenzymes B6 and B12 and the cosubstrate folate. Lifestyle factors, age, sex, acute and chronic illness, vitamin deficiency and certain drugs may elevate homocysteine concentrations. Vitamin B supplementation, especially folic acid, is an effective treatment of hyperhomocysteinemia. Clinical trials are required to confirm the potential benefit of lowering homocysteine in regard of the development and progression of atherosclerotic vascular disease. The relevance of hyperhomocysteinemia as a risk factor for atherosclerosis, in contrast to the classical triad of risk factors, namely hypercholesterolemia, smoking and hypertension, is still unknown. Furthermore, a lack of standardized analytical methods for the determination of both homocysteine and blood folate renders the evaluation of studies and clinical data difficult. Therefore, at present, diagnosis and treatment is only recommended in high-risk patients (strong family history of premature atherosclerosis or arterial occlusive disease, especially in the absence of other risk factors, as well as in members of their families) with hyperhomocysteinemia.

Arteriosclerosis↗
PubMed2000

[Unaltered homocysteine levels during simvastatin therapy].

Homocysteinemia is regarded as a risk factor for vascular disease. Several risk factors and diseases, but also various drugs, amongst them some lipid lowering medications, have been shown to increase plasma homocysteine concentrations. We therefore assessed the influence of simvastatin on plasma homocysteine levels in 57 patients suffering from severe familial heterozygous hypercholesterolemia. After 1, 3 and 6 months of simvastatin therapy plasma homocysteine levels did not show any change compared to the levels before therapy. Males had typically higher homocysteine levels than females and concentrations in smokers were in most subgroups significantly higher than in non-smokers. No difference in patients taking either 20 or 40 mg simvastatin was apparent and no correlation to the lipid lowering action was found. These findings indicate that in contrast to a number of other lipid lowering agents, simvastatin does not affect plasma homocysteine levels.

Adult↗
PubMed2000

Influence of acetylsalicylic acid on oxidation of native and glycated low-density lipoprotein.

It is generally accepted that oxidation of low-density lipoproteins (LDL) is a causal factor in the development of atherosclerosis. Non-enzymatic glycosylation of LDL, i.e."glycation", plays a central role in late complications of diabetes mellitus and may initiate and/or accelerate the oxidation process. Therefore, the inhibition of this processes is of major therapeutic relevance. The influence of acetylsalicylic acid (ASA) on the oxidation of native and glycated LDL was studied in vitro. LDL (0.25 mg protein/ml ) was oxidatively modified with 5.0 microM CuSO4. Only at "supratherapeutical" ASA concentrations in the range 0.06-2.0 mg /ml we found a significant concentration-dependent inhibition of LDL oxidation both for native and glycated LDL, which was from 0.2 mg/ml upwards significantly more marked for native LDL than for glycated LDL. The maximal inhibitory effect occurred at 2.0 mg/ml with 89.6% inhibition of LDL-oxidation for native LDL and 64.4% for glycated LDL. At 0.2 mg/ml ASA the respective inhibitory values were 38.5% and 31.0%. For glycated LDL the ASA doses of maximal- and approximately 50%-inhibition, as found for native LDL, were chosen to investigate the inhibitory effect on 2,4,8 and 24 hours oxidation of glycated LDL to monitor the time-dependency of inhibition by ASA. This revealed that ASA only delayed, not permanently inhibited LDL oxidation.

Adult↗
PubMed2000

Successful eradication of Helicobacter pylori as determined by ((13))C-urea breath test does not alter fibrinogen and acute phase response markers.

In this study we examined in 100 patients testing positive for Helicobacter pylori infection whether successful eradication therapy with pantoprazole, clarithromycin, and metronidazole alters fibrinogen and other acute phase response markers. Of 100 patients, only 11 showed a fibrinogen level above 300 mg/dL. Successful eradication proven by the 13C-urea breath test does not alter acute phase response markers. These findings indicate that Helicobacter pylori infection is unlikely to affect atherosclerosis unfavourably via acute phase response.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Influence of drugs on myocardial iodine-123 metaiodobenzylguanidine uptake in rabbit myocardium.

About 15 years ago, iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging was introduced for the evaluation of myocardial sympathetic nerve function. Two uptake mechanisms for MIBG have so far been identified: uptake type I, a saturable, energy-dependent mechanism, and uptake type II, a non-saturable, energy-independent mechanism. We incubated isolated rabbit myocardial tissue samples with 123I-MIBG in order to assess the uptake characteristics and the influence of varying incubation conditions. Furthermore, we examined the effects of several drugs and uptake inhibitors on the myocardial uptake of MIBG. The in vitro myocardial uptake of MIBG reached a steady plateau at 23.87%+/-3.63% after 1 h, i.e. a concentration gradient of 10, in a thermo-independent manner within a concentration range from 1.5 to 1500 microM. This indicates an unsaturable uptake process in the tested concentrations. Preincubation with the following drugs caused a significant inhibitory effect on myocardial MIBG uptake: haloperidol, levomepromazine, metoprolol, labetalol and clomipramine. According to our findings, the uptake mechanism seems to be an unspecific process, but the concentration gradient of 10 makes passive diffusion unlikely. Further studies with uptake-II-blocking substances as well as with isolated myocardial cells will be needed to clarify the nature of the myocardial MIBG uptake mechanism.

3-Iodobenzylguanidine↗
PubMed2000

Accumulation of oxidized LDL in human semilunar valves correlates with coronary atherosclerosis.

OBJECTIVE: Recent data indicate that oxidized low-density lipoprotein (ox-LDL) has several proatherogenic effects, e.g. induction of macrophage chemoattractants, adhesion molecules, cytokines, type-1 plasminogen activator inhibitor and platelet-derived growth factor A-chain by smooth muscle cells. Therefore, ox-LDL has been utilized as a marker of oxidative modification of proteins in atherosclerosis. Because heart valves consist of smooth muscle cells, fibroblasts and endothelial cells, and because valvular disease and coronary atherosclerosis could result from similar biological processes, we investigated ox-LDL accumulation in isolated aortic and pulmonary valves and coronary arteries from patients with angiographically proven coronary heart disease (CHD, n = 19), patients with idiopathic congestive heart failure (IDCM = idiopathic dilated cardiomyopathy, n = 20), and transplant donors. METHODS: Masson-Goldner staining and immunohistochemistry utilizing anti ox-LDL and CD68 were performed on paraffin sections of freshly isolated semilunar valves. Data were analyzed by digital image planimetry and by visual scoring of staining intensity. RESULTS: Ox-LDL immunoreactivity was identified in the vascular aspect of the attachment line, in the deep valve stroma, and in the ventricular and vascular endothelium of the semilunar valves, colocalizing with macrophages. Valvular ox-LDL area was significantly increased in CHD-patients (P < 0.03) and IDCM-patients (P < 0.04) compared with controls. More ox-LDL was accumulating in the pulmonary valves than in the aortic valves (P = 0.04) as assessed by area and staining intensity. Valvular ox-LDL area in pulmonary valve and aortic valve was significantly correlated with ox-LDL accumulation in the intimal layer (P < 0.001) and medial layer (P < 0.001) of coronary arteries from the same patients. CONCLUSION: The data suggest that the biological process leading to ox-LDL accumulation in coronary atherosclerosis also involves heart valves. Therefore, accumulation of the oxidative stress marker ox-LDL in heart valves illustrates atherosclerosis as an additional mechanisms accelerating valvular degeneration in these patients.

Aged↗
PubMed2000

Prevalence and relevance of thyroid dysfunction in 1922 cholesterol screening participants.

Controversy persists about the role of subclinical hypothyroidism in hypercholesterolemia. This study aimed to assess in a clinically healthy, middle-aged population of employees the prevalence of thyroid function disorders and their relation to demographic variables and cardiovascular risk factors. 1922 (former) employees were screened with follow-up of newly identified cases of undiagnosed (subclinical) hypothyroidism and hyperthyroidism. Thyroid stimulating hormone (TSH), prevalence and course of (subclinical) hypo- and hyperthyroidism and their relation to cardiovascular risk factors (cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, smoking, systolic and diastolic blood pressure) were assessed. The prevalence of newly diagnosed subclinical hypothyroidism (cut-off TSH concentration: 4.0 mU/L) was 1.1% (17 women and 5 men) with a mean TSH concentration of 7.37 (95% CI 5.18-9.56) mU/L. No case of overt hypothyroidism could be diagnosed. Elevated levels of antibodies to microsomal or thyroglobulin antigens were detected in six subjects with subclinical hypothyroidism (27.3%). Fifteen subjects (0.8%, 13 women and 2 men) had TSH concentrations below 0.1 mU/L. The cardiovascular risk profile of subjects with mild subclinical hypothyroidism was not different from subjects with normal TSH levels. The prevalence of subclinical hypothyroidism was 0.8% in normocholesterolemic (cholesterol <5.2 mmol/l) and 1.4% in hypercholesterolemic subjects (n.s.). One woman each with the subclinical form of the disease developed hypothyroidism or hyperthyroidism after 21 and 11 months of follow-up, respectively. Subclinical hypothyroidism and subclinical hyperthyroidism were rarely observed in a target group for coronary heart disease prevention. Mild subclinical hypothyroidism was not associated with any adverse cardiovascular risk profile. These results argue against indiscriminate measurements of TSH concentrations in clinically healthy subjects either with normocholesterolemia or hypercholesterolemia.

Adult↗
PubMed2000

99m-Tc-tetrofosmin scintigraphy for the evaluation of suspicious palpable and non-palpable breast lesions.

PURPOSE: To assess the value of 99m-Tc-tetrofosmin (tetrofosmin) scintigraphy in patients with palpable and nonpalpable breast lesions. PATIENTS AND METHODS: Prospective, blinded trial. One hundred and fifty-nine consecutive patients with 163 breast lesions detected by clinical examination and mammography were included. Tetrofosmin scintigraphy of the breast was performed additionally to the regular diagnostic procedure. Using histologic assessment as the golden standard, sensitivity, specificity, positive and negative predictive value for tetrofosmin scintigraphy of the breast were assessed. RESULTS: Overall sensitivity and specificity were 82% and 84%. The sensitivity for palpable tumors (65%) was 93% compared to 62% for non-palpable breast lesions. Malignant lesions were nearly twice as big as benign lesions (31.5 mm +/- 2.4 vs. 16.9 mm +/- 2.4). Specificity, positive and negative predictive value (84%, 89%, and 66%) did not differ significantly in palpable versus non-palpable tumors. Of malignant tumors 18% were found false negative by tetrofosmin scintigraphy. CONCLUSION: The results suggest that tetrofosmin scintigraphy is a valuable tool for the evaluation of palpable breast cancer. In patients with non-palpable tumors, tetrofosmin scintigraphy may not add to the work-up of patients with breast cancer due to a low sensitivity rate.

Adult↗
PubMed2000

Isoprostanes quickly normalize after quitting cigarette smoking in healthy adults.

BACKGROUND: Isoprostanes and in particular 8-epi-PGF2 alpha have been claimed as a useful measure for invivo oxidation injury. While smokers show elevated 8-epi-PGF2 alpha the behaviour during quitting smoking is unknown. METHODS AND RESULTS: We determined 8-epi-PGF2 alpha in 7 healthy adults ready to quit smoking in plasma, serum and urine by means of an enzyme immunoassay after extraction and purification before quitting smoking and during a follow-up period of 4 weeks. After quitting smoking, 8-epi-PGF2 alpha shows a rapid decline within a few days almost completely normalizing within 4 weeks. CONCLUSION: The cigarette-smoking associated invivo oxidation injury almost completely disappears within 4 weeks of quitting smoking.

Adult↗