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H Sinzinger

Publications and source records attributed to H Sinzinger.

At least 73 records · Page 4Linked to original sources
PubMed2000

Prostaglandin E1-therapy reduces circulating adhesion molecules (ICAM-1, E-selectin, VCAM-1) in peripheral vascular disease.

BACKGROUND: It has been postulated that adhesion molecules (AM) may be involved in development and progression of human atherosclerosis. We examined whether prostaglandin (PG) E1 affects circulating levels of the AM (ICAM-1, VCAM-1 and E-selectin) in peripheral vascular disease (PVD) patients. METHODS AND RESULTS: AM are significantly (p < 0.01) increased in PVD (n = 65) as compared to controls (n = 31). There was no influence of risk factors. 26 PVD-patients received 2 different schemes of PGE1-therapy (group A [n = 17]; 5 ng PGE1/kg/min x 6 h x 5 d x 4 wk; group B [n = 9]; 60 micrograms PGE1/2 h x 5 d x 2 wk). PGE1 decreases all the AM significantly (p < 0.01) using both therapeutic schemes. Stopping PGE1-therapy reverses values within about 4 weeks. Details on therapeutic regimens (dose, duration, route, etc.) and individual response still need to be assessed. CONCLUSION: Our results indicate that PGE1-treatment of PVD is associated with a significant benefit on circulating AM. These findings are in line with the described anti-inflammatory actions of PGE1 and may represent a further contributing factor to the great variety of beneficial actions of PGE1 on human atherosclerosis.

Aged↗
PubMed2000

Eicosanoid generation and responsiveness of human lymphatics in hyperlipoproteinemia.

In this work, the oxidation injury in hyperlipoproteinemia (HLP) was determined by measuring the isoprostane 8-epi-prostaglandin (PG) F2alpha in human lymphatics, lymph fluid, plasma, serum and urine. Lymphatics from 6 patients with HLP generated less PGI2 and contained more 8-epi-PGF2alpha as compared to 6 normolipemics without risk factors. Likewise, plasma (29.3 vs 19.7 pg/ml), lymph fluid (137.3 vs 65.3 pg/ml), serum (286.7 vs 204.1 pg/ml) and urinary (360.8 vs 241.0 pg/mg creatinine) values of 8-epi-PGF2alpha in HLP (as compared to normolipemics) were significantly elevated. Lymphatics from HLP showed an enhanced contractile response, less 14C-arachidonic acid conversion to PGI2 and less PGI2-formation upon various stimuli compared to normolipemics of comparable age. These findings indicate that HLP-induced oxidation injury, resulting in an altered (iso-)eicosanoid production and function, may also significantly affect (patho-) physiology of lymphathics.

Adult↗
PubMed2000

LDL-apheresis decreases plasma levels and urinary excretion of 8-epi-PGF2alpha.

Isoprostanes (IP) generated during free radical catalyzed oxidation injury have been claimed as a reliable indicator of oxidative stress in vivo. In particular, they are formed during LDL-oxidation. Vascular content, plasma levels and urinary excretion of IP were reported to be elevated in hypercholesterolemia. We therefore assessed the values of the IP 8-epi-PGF2alpha in plasma and urine in nine patients (7 males, 2 females) suffering from severe heterozygous hypercholesterolemia before and after LDL-apheresis as well as during the interval. LDL-apheresis caused a significant (P<0.01) drop in 8-epi-PGF2alpha in plasma and urine. The respective values in smokers (n = 4) were significantly (P<0.01) higher as compared to non-smokers. No sex difference was seen. Together with the findings of a parallel decrease in oxidized LDL, these data show a significant benefit of LDL-apheresis reducing in vivo oxidation injury. This benefit may at least partly contribute to the clinical improvement seen in the patients treated.

Adult↗
PubMed2000

The effects of glycation/glycoxidation on the liberation of 8-epi-PGF2alpha from low density lipoprotein during its in vitro oxidation.

In individuals suffering from diabetes mellitus, low-density lipoprotein (LDL) can undergo glycoxidation, both the surface protein and the unsaturated fatty acids in the particle core experiencing oxidative damage. In these patients, plasma levels of glycated(g)/glycoxidated(go) low-density lipoprotein and of 8-epi-PGF2alpha (8-IP), a relatively stable peroxidation product of arachidonic acid, are increased. This study reports on the modified oxidation of gLDL and goLDL by human umbilical vein endothelial cells or by copper cations in the absence of cells. In both systems, glycated LDL was found to be more easily oxidized than either nLDL or goLDL. In addition, liberation of 8-IP from glycoxidated LDL is significantly reduced, because a large amount of 8-IP is already formed during long-term glycation of LDL in the absence of metal chelators, i.e. during glycoxidation. From these in vitro results we conclude, that 1) gLDL is more prone to cell-mediated oxidation than native or goLDL and 2) the increased in vivo plasma levels of 8-IP observed in diabetes mellitus could be due to prolonged LDL-glycoxidation liberating continuously significant amounts of 8-IP.

Adult↗
PubMed2000

Why is glycated LDL more sensitive to oxidation than native LDL? A comparative study.

It is well established that oxidative modification of low-density lipoprotein (LDL) plays a causal role in human atherogenesis and the risk of atherosclerosis is increased in patients with diabetes mellitus. To examine the influence of different agents which may influence LDL-glycation and oxidation, experiments including glycation with glucose, glucose 6-phosphate, metal chelators (EDTA) and antioxidants (BHT) were performed. The influence of time dependence on the glycation process and the alteration of the electrophoretic mobility of LDL under diverse glycation and/or oxidation conditions was also investigated. The formation of conjugated dienes and levels of lipid peroxides in these different LDL-modifications were estimated. The copper-induced oxidation of LDL in vitro was determined by measurement of thiobarbituric acid reactive substances (TBARS) and expressed as nmol MDA/mg of LDL protein. We found that glycated LDL is more prone to oxidation than native LDL. Using native LDL, the maximal oxidation effect was found to reach a value of 49.72 nmol MDA/mg protein after 8 h. The maximum oxidation of the 31 days, glycated LDL with glucose was 71.76 nmol MDA/mg protein amounting to 144.33% of the value found for native LDL. In the case of glucose 6-phosphate glycation, the maximum oxidation under the same conditions amounted to 173.77% of the value found for native LDL. To measure the extent of glycation, fluorescence of advanced glycation end products (AGEs) was determined (370 nm excitation and 440 nm emission). The most potent glycation agent was glucose 6-phosphate leading to the formation of very high amounts of AGEs. This process was promoted in the absence of EDTA, which prevents the oxidative cleavage of modified Amadori products (ketoamines) to AGEs. We therefore conclude that both processes, glycation and oxidation, result in the modification of LDL. The lower the glycation-rate (+/- EDTA) as measured by relative fluorescence units RFU (generation of AGEs), the lower the additional oxidation rate after glycation as measured by TBARS (generation of MDA equivalents). Glycation and/or oxidation change the electrophoretic mobility of LDL.

Adult↗
PubMed2000

Association of lipoprotein(a), prostaglandin I(2)--synthesis stimulating plasma factor, biological half-life of prostaglandin I(2)and high-density lipoproteins in HIV-1 infection of different stages.

Patients with human immunodeficiency virus show increased atheroembolism and premature arterial events (stroke, myocardial infarction), but no increased venous thromboembolism. This paper describes an association of elevated lipoprotein(a), a decreased prostaglandin I(2)(PGI(2)) synthesis stimulating plasma factor, diminished PGI(2)-stability in plasma and decreased high-density lipoprotein-cholesterol and apolipoprotein A. It is unclear to what extent these biochemical findings represent an acute phase reaction only or a disturbance in the prostaglandin system. Definitely, they are resulting in severe hemostatic imbalance decreasing local PGI(2)-availability with a dramatic reduction in the cytoprotective capacity favouring the onset of premature arterial events seen in some of the patients.

6-Ketoprostaglandin F1 alpha↗
PubMed2000

Short-term atorvastatin treatment improves endothelial function in hypercholesterolemic women.

Endothelial dysfunction represents the earliest stage of atherosclerosis and is usually present in hypercholesterolemia. Treatment with statins has been shown to normalize endothelial function in middle-aged men with hypercholesterolemia. We evaluated the effect over time of atorvastatin on the endothelial reactivity in postmenopausal hypercholesterolemic women (mean age, 58 +/- 6 years), receiving atorvastatin, 10 mg daily (n = 20) or American Heart Association step 1 diet (n = 10) for 8 weeks. Lipid profile and brachial artery flow-mediated vasodilation (FMV) were determined at baseline and after 1, 2, 4, and 8 weeks. FMV increased progressively in subjects treated with atorvastatin, and the difference was significant (p < 0.05 vs. baseline) after the second week (baseline 3.8 +/- 3%; first week, 4.8 +/- 3%; second week, 9.2 +/- 3%; fourth week, 11.0 +/- 3%; eighth week, 11.7 +/- 3%). No significant changes were observed in subjects receiving diet (baseline, 3.1 +/- 4%; first week, 2.4 +/- 2%; second week, 2.9 +/- 2%; fourth week, 3.1 +/- 2%; eighth week, 3.3 +/- 2%; p = NS). In the atorvastatin group, low-density lipoprotein (LDL) cholesterol showed a significant decrease since the first week (baseline, 228 +/- 37 mg/dl; first week, 171 +/- 32; second week, 147 +/- 27; fourth week, 139 +/- 29; eighth week, 135 +/- 27; all p < 0.05). In the control group, LDL cholesterol showed a smaller but significant (p < 0.05) reduction after the second week (baseline, 226 +/- 17 mg/dl; first week, 225 +/- 16; second week, 220 +/- 17; fourth week, 203 +/- 27; eighth week, 198 +/- 27). In conclusion, hypercholesterolemic women treated with atorvastatin show a significant improvement in endothelial reactivity after as early as 2 weeks of therapy. The extent to which these beneficial effects are attributable to cholesterol reduction or to a direct effect of the drug remains to be established.

Analysis of Variance↗
PubMed2000

Radiation synovectomy using 165Dy ferric-hydroxide and oxidative DNA damage in patients with different types of arthritis.

UNLABELLED: Radiation synovectomy is an effective treatment for chronic synovitis refractory to pharmacological treatment in patients with rheumatoid or seronegative arthritis. Concerns persist about possible radiation-induced cytogenetic damage after radiation synovectomy leading to recommendations to use this technique only in the elderly. Micronucleus (MN) frequency in lymphocytes and urinary excretion of 8-hydroxy-2'-deoxyguanosine (8OHdG) as an indicator of cellular oxidative DNA base damage are biomarkers of radiation-induced cytogenetic damage. The course of both biomarkers was studied in patients with different types of chronic synovitis undergoing radiation synovectomy with very short-lived 165Dy-ferric-hydroxide (DFH). METHODS: Radiation synovectomy of the knee was performed in 13 men and 12 women (mean age, 44+/-15 y) using a mean activity of 9.48+/-1.65 GBq 165Dy-DFH in 27 consecutive treatments. MN frequency in lymphocytes and urinary excretion of 8OHdG, measured by high-performance liquid chromatography, were assessed before and 4 (MN only) and 20 h after radiation synovectomy. RESULTS: Urinary excretion of 8OHdG in patients (in micromol/mol creatinine; pretreatment mean, 3.1+/-3.4; median, 2.27) was not significantly different from that in healthy volunteers (mean, 2.0+/-1.2; median, 1.87) and not altered by radiation synovectomy (post-treatment mean, 2.5+/-1.5; median, 2.04, NS). An increase in 8OHdG levels after radiation synovectomy of more than 1 SD was found in only 1 patient, who experienced leakage to the lymph nodes but who already had elevated urinary 8OHdG levels before treatment. The frequency of MN/500 binucleated cells (BNCs) was slightly lower in patients (pretreatment mean, 4.3+/-2.6; median, 4.25) than in healthy volunteers (mean, 5.4+/-2.3; median, 5.3) and did not significantly change after therapy, either (4-h post-treatment mean, 3.9+/-2.1, median, 3.8; 20-h post-treatment mean, 4.1+/-2, median 3.8 MN/500 BNC). In 22 of 27 treatments, no leakage to nontarget organs could be monitored, whereas leakage to the local lymph nodes and the liver was detected after 5 treatments. CONCLUSION: Radiation synovectomy using 165Dy-DFH causes no significant radiation burden to most patients as indicated by the absence of adverse changes in levels of biomarkers of cytogenetic damage and a low incidence of leakage. These data suggest that the risk of malignancy may not be elevated.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

Use of 99mTc-furifosmin scintigraphy--planar and SPECT--to evaluate suggestive palpable and nonpalpable breast lesions.

UNLABELLED: Our objective was to evaluate the role of 99mTc-furifosmin scintigraphy--planar and SPECT--in discriminating benign from malignant breast disease. METHODS: The trial was prospective, open, and diagnostic. We recruited 30 consecutive patients with 14 palpable and 16 nonpalpable breast lesions. After receiving informed consent, we injected 555-640 MBq 99mTc-furifosmin intravenously in the arm contralateral to the breast lesion. Planar imaging and SPECT were performed. All patients underwent excision of the tumor within 2 wk. Using histology as the gold standard, we calculated sensitivity, specificity, and positive and negative predictive values for 99mTc-furifosmin in planar and SPECT technique. RESULTS: For 18 malignant and 12 benign breast lesions, a sensitivity of 50% for planar imaging and 72% for SPECT was seen. Specificity and positive and negative predictive values were 83%, 82%, and 53%, respectively, for planar imaging and 50%, 68%, and 55%, respectively, for SPECT. For the 14 palpable tumors (10 malignant, 4 benign), which averaged 17+/-10 mm in size (size range, 4-45 mm), a sensitivity of 60% for planar imaging and 80% for SPECT was achieved. Sixteen lesions were not palpable (median size, 9+/-3 mm [size range, 4-13 mm]). In this subgroup, 99mTc-furifosmin scintigraphy yielded a sensitivity of 37% for planar and 62% for SPECT technique (P>0.05). CONCLUSION: 99mTc-furifosmin scintigraphy is not a potent competitor to established scintigraphic procedures. In comparing this tracer with 99mTc-sestamibi and 99mTc-tetrofosmin, we cannot recommend 99mTc-furifosmin for the diagnosis of breast cancer.

Breast Diseases↗
PubMed2000

Eicosanoid production and lymphatic responsiveness in human cigarette smokers compared with non-smokers.

Leg lymphatic segments were isolated from 10 patients (4 cigarette smokers and 6 non-smokers) undergoing conventional lymphography. Prostaglandin (PG) levels and PG synthesis in the lymphatics and in a variety of body fluids and the effects of eicosanoids on lymphatic contractility were determined. Leg lymphatics from 4 smokers generated less PGI2 and contained more 8-epi-PGF2 alpha when compared with leg lymphatics in 6 non-smokers. Similarly, levels of 8-epi-PGF2 alpha in smokers compared with non-smokers were higher in plasma (28.6 cf 19.7 pg/ml), leg lymph (146.7 cf 65.3 pg/ml), serum (299.0 cf 204.1 pg/ml), and urine (473.4 cf 241.0 pg/mg creatinine). Lymphatics from smokers also showed a higher contractile response, less 14C-arachidonic acid conversion to PGI2 and less PGI2-formation with various stimuli compared with non-smokers. Together these findings suggest that smoking induces oxidation injury, promotes altered (iso-)eicosanoid production and impacts on the function and dysfunction of peripheral lymphatics under normal circumstances and in a variety of clinical disorders.

Eicosanoids↗
PubMed2000

Prostaglandin synthesis in human lymphatics from precursor fatty acids.

(Iso)-eicosanoids appear to play a pivotal role in lymphatic contractility. Because prostaglandin (PG)I2, an arachidonic acid (20:4) metabolite, is a key substance generated by human lymphatics, both from exogenous and endogenous substrates, it is reasonable to assume that altered nutritional intake of precursor fatty acids (FA) influences formation of respective eicosanoids qualitatively and quantitatively, and thereby modify its biological effects on human lymphatics. We, therefore, examined the effect of 2 other FA-precursors, dihomo-gamma-linolenic (20:3) and eicosapentaenoic acid (20:5) on the formation of the respective PG-metabolites in human lymphatics removed from the legs in patients undergoing amputation after traumatic injury. 20:3 and 20:5 were poorer substrates to form PGs. Because these PGs exert different biological actions and their synthesis may be altered by vascular environmental risk factors such as cigarette smoking, diabetes mellitus, hyperlipidemia, and availability of FA precursors and therefore nutrition, PGs may profoundly modulate the lymphatic contractile response under a variety of circumstances. The full effect of all the formed compounds of the 1- and 3-series PGs on lymph vessel contractility, however, still needs to be tested.

Adult↗
PubMed2000

Uptake of 99mTc-MIBI and 99mTc-tetrofosmin into malignant versus nonmalignant breast cell lines.

UNLABELLED: The kinetics and cellular uptake of 99mTc-2-hexakis 2-methoxyiso-butyl-isonitrile (MIBI) and 99mTc-1 ,2-bis[bis(2-ethoxyethyl)phosphino]ethane (tetrofosmin) into malignant versus nonmalignant human breast cell lines were investigated and compared. METHODS: At specific intervals after incubation at 37 degrees C and 22 degrees C with 99mTc-MIBI or 99mTc-tetrofosmin, the uptake characteristics of radiotracers into human adenocarcinoma breast cell lines MCF-7 and SK-BR-3 and human breast, nontumor cell line HBL-100 were assessed. RESULTS: The uptake of 99mTc-MIBI and 99mTc-tetrofosmin was lower at an incubation temperature of 22 degrees C than that at 37 degrees C in the 3 cell lines. In MCF-7 and in SK-BR-3 cells the uptake of 99mTc-MIBI was significantly higher than the uptake of 99mTc-tetrofosmin. The uptake of 99mTc-MIBI was significantly higher into MCF-7 and SK-BR-3 cells than that into HBL-100 cells. In comparison with HBL-100 cells, uptake of 99mTc-tetrofosmin into SK-BR-3 cells was significantly higher, whereas uptake into MCF-7 cells was similar. CONCLUSION: In vitro data suggest that 99mTc-MIBI may be a better tracer than 99mTc-tetrofosmin for discrimination between malignant and nonmalignant breast disease.

Adenocarcinoma↗
PubMed2000

Comparative 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin uptake in human soft tissue sarcoma cell lines.

The uptake characteristics of technetium-99m hexakis-2-methoxyisobutylisonitrile (MIBI), 99mTc-tetrofosmin and 99mTc-furifosmin in human soft tissue sarcoma cell lines were investigated and compared. After 10-120 min of incubation at 37 degrees C, 32 degrees C and 22 degrees C with 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin, the kinetics of cellular uptake of these tracers in human soft tissue sarcoma cells SW 684 (fibrosarcoma), SW 872 (liposarcoma), SW 982 (synovial sarcoma) and SW 1353 (chondrosarcoma) was assessed. The uptake of 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin was temperature dependent. The kinetics of uptake of 99mTc-MIBI and of 99mTc-tetrofosmin was similar between fibrosarcoma and liposarcoma cells, as well as between synovial sarcoma and chondrosarcoma cells. 99mTc-furifosmin showed similar uptake kinetics in all cell lines. The uptake of 99mTc-furifosmin was, however, significantly higher in liposarcoma than in the other cells. The data indicate that the cellular uptake of 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin is dependent on cellular metabolic activity.

Cell Survival↗
PubMed2000

Isoprostanes in atherosclerosis.

Isoprostanes (IP) are a new family of compounds formed during oxidation injury. 8-epi-prostaglandin (PG) F2alpha, a vasoconstrictory and mitogenic substance, is increased in hyperlipidemia in blood and urine as well as at the vascular level in the intima, in particular along foam cells. Similarly, cigarette smoking is associated with an immediate increase in 8-epi-PGF2alpha and a quick drop after quitting. Also diabetes and even the more a combination of risk factors (for the development of atherosclerosis) results in increased 8-epi-PGF2alpha in various compartments. Others, such as sex, age, hypertension and obesity were of minor influence. These findings further indicate, that in-vivo oxidation injury as reflected by increased IP may play a relevant role in atherogenesis. IP may serve as useful markers to assess oxidation injury at a local level.

Adolescent↗
PubMed1999

Effects of fish oil supplementation on platelet survival and ex vivo platelet function in hypercholesterolemic patients.

Little is known about the effects of dietary supplementation on platelet survival with low doses of n-3 and n-6 fatty acids in patients with hypercholesterolemia. The effects of a 6-week intervention with fish oil capsules (daily intake: 216 mg eicosapentaenoic acid, 140 mg docosahexaenoic acid, 390 mg gamma-linolenic acid, and 3480 mg linoleic acid) on in vivo platelet survival (111 In-oxine labeled platelets) and on ex vivo markers of platelet activation were investigated in a placebo-controlled, double-blind study with 26 hypercholesterolemic patients. In vivo platelet survival increased in the fish oil group (T) from a mean of 159+/-14 hours to a mean of 164+/-12 hours (p=0.025), whereas it remained unchanged in the placebo (P) group (T vs. P; p=0.055). Ex vivo, thromboxane B2 decreased from a mean of 225+/-16 to 212+/-21 ng/mL (p=0.003) in T but did not change in P (T vs. P: p=0.002). Malondialdehyde formation was lowered significantly by fish oil supplementation from a mean of 5.49+/-1.3 to 5.12+/-1.05 nM/10(9) platelets, p=0.005, as compared with P (T vs. P; p=0.018). The trendwise decrease in 11-DH-thromboxane B2 plasma levels was not significant nor was the increase in platelet sensitivity to prostaglandin I2 by fish oil. Baseline platelet survival in patients with hyperlipoproteinemia type IIa was not different from those with hyperlipoproteinemia IIb and response to treatment in terms of platelet activation markers was not either. The changes in platelet activation parameters in T were associated with significant reductions in cholesterol (-2.9%), low density lipoprotein cholesterol (-3.5%), and triglycerides (-12.4%). Both ex vivo and in vivo platelet activation parameters exhibited signs of decreased activation by a 6-week diet supplemented with n-3 and n-6 fatty acids, which might be beneficial in reducing atherothrombotic risk, in patients with hyperlipoproteinemia type IIa and IIb.

Blood Platelets↗
PubMed1999

The isoprostane, 8-epi-PGF2 alpha, is accumulated in coronary arteries isolated from patients with coronary heart disease.

OBJECTIVE: In the present study we wanted to know whether 8-epi-PGF2 alpha, which belongs to the class of isoprostanes formed by free radical-mediated peroxidation of arachidonic acid and arachidonyl-containing phospholipids, is enriched in isolated coronary arteries of patients suffering from coronary heart disease (CHD, n = 23) who received allograft heart transplants as compared to vessels derived from patients with dilative cardiomyopathy (CMP, n = 19) or from healthy heart donors (controls, n = 6). METHODS: Sections from the isolated coronary arteries were analysed by semiquantitative immunohistochemistry by determining the area and intensity of positive reaction for 8-epi-PGF2 alpha in the vascular intima and media. In addition, the 8-epi-PGF2 alpha content was determined using a specific immunoassay after extraction and purification. RESULTS: The immunohistochemical results indicated that 8-epi-PGF2 alpha is significantly enriched in arteries from patients suffering from CHD as compared to CMP (P < 0.0001). In controls, significantly less immunostaining was observed. Furthermore, a significant positive correlation between semiquantitative immunohistochemistry and radioimmunological determination was observed too. CONCLUSIONS: From our findings we conclude that 8-epi-PGF2 alpha is especially accumulated in coronary arteries from CHD patients and therefore is likely to be involved in atherogenesis.

Analysis of Variance↗
PubMed1999

Examination of co-complexes for radiolabeling of platelets in positron emission tomographic studies.

Oxine, tropolonate, and mercaptopyridine-N-oxide (MPO) have been widely used with 111In for platelet labeling. The use of positron emission tomography (PET) radioisotopes for platelet labeling would offer a higher sensitivity and resolution over conventional imaging. The medium half-life PET radioisotope 55Co (t1/2 = 18.2 hours) would enable quantitative uptake and cell kinetic studies with radiolabeled platelets. To identify the optimal complex for radiolabeling of platelets with 55Co, we investigated the platelet uptake of 57Co-oxine, 57Co-tropolonate, and 57Co-MPO in varying different parameters. The platelet uptake of Co-complexes was generally low (5-12%), dependent on time and temperature of incubation and density of platelets but independent of the amount of radioactivity. These findings are not promising for potential PET application.

Adult↗