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Biomedical subjects

H Sinzinger

Publications and source records attributed to H Sinzinger.

At least 37 records · Page 2Linked to original sources
PubMed2002

Enhanced accumulation of the isoprostane, 8-epi-PGF2 alpha, in human aortic and pulmonary valves of patients with coronary heart disease.

The aim of the present study was to investigate whether the isoprostane 8-epi-PGF2 alpha differently accumulates in semilunar valves of patients suffering from coronary heart disease (CHD, n = 19) as compared to valves from healthy heart donors (controls, n = 6). Sections from isolated aortic and pulmonary valves were analyzed by semiquantitative immunohistochemistry. The 8-epi-PGF2 alpha-content was determined by using a specific radioimmunoassay. The accumulation of 8-epi-PGF2 alpha in both valves was higher in CHD-patients in comparison to controls (Aortic valves: 36.49 +/- 11.26% vs. 15.78 +/- 3.04%; pulmonary valves: 46.79 +/- 9.80% vs. 14.99 +/- 3.57%). The results from the radioimmunoassay revealed comparable findings in both groups (CHD vs. controls: 395.95 +/- 86.09 vs. 139.50 +/- 47.46 pg/mg protein in the aortic valves and 430.47 +/- 76.30 vs. 147.33 +/- 53.84 pg/mg protein in pulmonary valves). Pulmonary valves seem to be more susceptible to oxidative stress than aortic valves as evidenced by a higher accumulation of 8-epi-PGF2 alpha in CHD patients. Considering the data presented in this study, we suggest that 8-epi-PGF2 alpha is a valuable indicator of oxidative injury in human semilunar valves.

Aged↗
PubMed2001

Calcium antagonists as inhibitors of in vitro low density lipoprotein oxidation and glycation.

The peroxidation step in lipid transformation is considered to be essential in the pathogenesis of atherosclerosis. Calcium antagonists (CA) appear to have antioxidant effects in addition to their potent vasorelaxant properties. In the present study, we compared the antioxidative efficacy of CA (amlodipine, lacidipine, nifedipine, isradipine, diltiazem, and semotiadil) in the copper-catalysed oxidation of low-density lipoprotein (LDL) with that of glycated(g)/glycoxidated(go) LDL. This issue is of great importance when considering the potential therapeutic use of antioxidant drugs in diabetes-associated vasculopathy. Oxidation of native LDL was inhibited most efficiently (>90%) by lacidipine and semotiadil in the concentration range 10(-4)-10(-3) M. We found, however, a dramatic decrease in antioxidant activity towards g/goLDL as compared to native LDL in all the CA tested. Only lacidipine significantly inhibited copper-mediated oxidation of g/goLDL in the whole concentration range tested (10(-5) M-10(-3) M). This probably resulted from the increased auto-oxidative potential introduced by early and advanced glycation end products (AGE) into the g/goLDL. We noted that coincubation of LDL with 10(-3) M CA and 0.5 M glucose under oxidative/non-oxidative conditions partially or fully restored the antioxidant capacity of the different CA to inhibit the subsequent copper-catalysed oxidation of the modified LDL. This is a clear indication that CA inhibit glycative or glycoxidative LDL changes during the preceding long-term glycation period. The notion that both oxidative changes and long-term glycation effects were reduced by CA was corroborated by fluorescence analysis, AGE-ELISA, quantitation of lipid peroxidation, and thiobarbituric acid reactive substance (TBARS) measurement of long-term g/goLDL. The strongest antioxidative effects during long-term glycation of LDL were seen with isradipine, lacidipine, nifedipine, and semotiadil. Diltiazem was the only CA that could not prevent TBARS formation in LDL during the long-term glycation period. In contrast, Amadori product formation, as measured by the generation of fructosamines, was not significantly reduced by any CA tested. Thus CA, like other antioxidants, significantly retard AGE formation, while initial glycation reactions, such as Amadori product formation, are only weakly inhibited.

Antioxidants↗
PubMed2001

Positive imaging of an inflammatory process at an arteriovenous access site with 111 Indium-labeled platelets.

Complications associated with the vascular access for hemodialysis represent one of the most important causes of morbidity among patients with renal replacement therapy. Early detection of arteriovenous fistula (AVF) dysfunction is of great interest. We present the case of a 70 year old woman who underwent 111In-oxine-labeled-platelet scintigraphy to evaluate thrombogenicity at 3 weeks and 3 months after surgery of a new AVF. In the first post-operative scintigraphy 4 hours after reinjection of autologous 111In-labeled platelets, enhanced focal activity was visible in the AVF projection which could not be detected after 24 hours. Since early platelet accumulation may reflect hyperemia in inflammation, this diagnosis was verified by anti-granulocyte antibody scintigraphy. The platelet scintigraphy performed 3 months later was negative, with persistence of sufficient AVF function. These data show an intense early accumulation of 111In-oxine-labeled-platelets in unspecific inflammation of an AVF.

Aged↗
PubMed2001

Methylene blue-enhanced stability of (99mTc)HMPAO and simplified quality control--a comparative investigation.

(99mTc)HMPAO is a radiopharmaceutical used for SPECT imaging of regional cerebral perfusion and for labeling cellular blood elements. The addition of methylene blue enhanced the stability of lipophilic (99mTc)HMPAO complex up to 3 h after reconstitution, 86.9+/-4.2% compared to 49.8+/-8.9% for the non-stabilised complex and persists over time (86.2+/-3.5% after 15 min compared to 78.2+/-4.0% after 3 h). The method widely used for estimation of radiochemical purity is a standard chromatographic procedure which is quite time-consuming taking about 30 min. Comparison of the more rapid and simple solvent extraction method with octanol, which needs only about 10 min to complete. showed a good correlation with the chromatographic method (84.4+/-4.4% compared to 89.1+/-4.3%). Using ethyl acetate as solvent instead of octanol gave a slightly higher extraction rate of the lipophilic complex (91.5+/-5.5% compared to 89.1+/-4.3%). Further, the ethyl acetate extraction method results in an overestimation, extracting partly secondary complex. It is confirmed, that the stability of the lipophilic (99mTc)HMPAO complex can be increased with methylene blue. The octanol extraction method, using higher extraction volume (up to 3 ml), is recommended as a fast and efficient approach for the quality control in daily clinical routine.

Acetates↗
PubMed2001

Isoprostane 8-epi-PGF2alpha is frequently increased in patients with muscle pain and/or CK-elevation after HMG-Co-enzyme-A-reductase inhibitor therapy.

BACKGROUND: Muscle pains with or without CK-elevation are among the most frequently observed side-effects in patients with hyperlipoproteinemia on various statins. The pathophysiological background, however, remains obscure. METHODS: We examined isoprostane 8-epi-PGF2alpha, a marker of in-vivo oxidation injury, in plasma, serum and urine in these patients at baseline, when muscle problems manifested and different time intervals after withdrawing the respective statin. A healthy control group and a group of untreated patients with hyperlipoproteinemia were run as controls. RESULTS: The majority of patients with muscular side-effects show elevated 8-epi-PGF2alpha in plasma and urine, whereas serum values were elevated only to a lesser extent. Stopping statin therapy or successfully changing to another member of this family of compounds resulted in a normalization of the values in all patients. CONCLUSION: These findings indicate a significant involvement of oxidative injury in the muscular side-effects of statins in patients suffering from hyperlipoproteinemia.

Adult↗
PubMed2001

Oral L-arginine administration attenuates postprandial endothelial dysfunction in young healthy males.

BACKGROUND: Endothelial dysfunction is considered the earliest stage of atherosclerosis. Postprandial phase is associated with a transient impairment of endothelial function concomitantly with the triglyceride-rich lipoprotein increase. This phenomenon may be explained by the oxidative burden induced by triglyceride-rich lipoproteins, reducing nitric oxide bioavailability. OBJECTIVE: To investigate the effect of a diet enriched with L-arginine, the substrate for nitric oxide synthesis on endothelial function in healthy volunteers. METHODS: Endothelial function (expressed as flow-mediated vasodilation (FMV) of the brachial artery), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, LDL-size, Lp (a) and reduced glutathione (GSH) were evaluated in seven healthy males (mean age 23 +/- 3 years) without cardiovascular risk factors. Measurements were made at baseline and 2, 4 and 6 h after a standardized oral fat load. L-arginine (6 g daily) was administered for 10 days. On the 11th day the oral fat load and the parameters examined previously at entry were repeated. RESULTS: After the first oral fat load, FMV significantly decreased at 2 and 4 h, and overlapped with the basal levels at 6 h. After L-arginine treatment, FMV significantly decreased at 2 h and normalized after 4 and 6 h. Triglycerides increased at 2 and 4 h and decreased after 6 h in both sets of observations relating to before and after L-arginine administration. GSH dropped 2 h after the fat load, both before and after L-arginine. Before L-arginine, FMV exhibited a significant correlation with triglycerides (r= -0.426, P= 0.024) and GSH (r=0.48; P=0.009). After L-arginine, FMV was related to GSH (r=0.39; P=0.03) but not to triglycerides (r= -0.12; P=0.52). CONCLUSION: Postprandial endothelial impairment is partly abolished by L-arginine administration. These data, which require confirmation, suggest the importance of dietary choice for atherosclerosis prevention even in young healthy subjects.

Adult↗
PubMed2001

Assessment of peripheral arterial vascular disease with radionuclide techniques.

Various radioisotopic imaging techniques for noninvasive detection of vessel stenosis and for functional investigation of reduced blood flow and follow-up have been developed during the last decade in peripheral vascular disease (PVD), with the aim of replacing invasive techniques and complementing standardized methods. Radionuclide assessment of PVD is divided into 2 major groups: imaging of perfusion and metabolic investigations. The measurement of arterial blood flow and muscle perfusion is intended to show the morphology, to evaluate the functional consequences of PVD, and to quantify the latter. The application of radiolabeled tracers was developed as a noninvasive alternative to angiography in morphologic imaging. Treadmill testing has been used to assess the functional effects of reduced blood flow in PVD where the onset of pain indicates the stage of disease, but the results can be confused by other symptoms. Scintigraphic measurement of muscle perfusion should detect insufficient nutritional blood flow in peripheral muscle and thus have a higher specificity for PVD than treadmill testing alone. Although there are very promising theoretical and experimental data in animals, the clinical use of radionuclide investigations is limited by different technical problems, such as methodologic differentiation between skin and muscle perfusion, the lack of controlled and prospective studies, and incomplete correlation with other standardized routine techniques. Among the great number of radioisotopic metabolic imaging techniques, only radiolabeled platelets and lipoproteins, to some extent, have shown a limited potential clinical use. Some other approaches seem to have a high potential from a theoretical point of view. They are limited, however, by a great number of problems. Correlation with sonographic or magnetic resonance imaging (MRI) findings may identify a potential metabolic value. Correlation with angiography reflecting the extent of the disease makes no sense. So far with PVD, neither radioisotopic perfusion studies nor metabolic imaging techniques are able to achieve a level of routine application or wider meaningful interpretation of the clinical condition of a specific patient. Competing techniques are easier to perform, less expensive, faster, more widely available, and do not carry the radiation burden. Positron emission tomography is still in its early stages of application, with great theoretical potential but at a high price. A great deal of work is still required to transform in vitro and experimental experience into more meaningful routine radioisotopic investigations in patients with PVD.

Animals↗
PubMed2001

Nuclear medicine and breast cancer: a review of current strategies and novel therapies.

While breast cancer is still increasing in frequency, new diagnostic procedures are now available to challenge existing procedures and to make diagnosis of breast cancer more accurate and reliable. Mammography remains the standard investigation to reveal disease in an asymptomatic population: it can also be used to diagnose breast cancer in symptomatic patients (e.g. those with palpable breast lumps) and for guiding fine needle aspiration (FNA). Because the majority of breast lumps are benign, the challenge is to distinguish benign from malignant lesions without the use of invasive methods and this has attracted nuclear medicine physicians and medical oncologists to investigate the role of scintigraphic procedures to identify which patients require FNA. This review attempts to shed light on the various scintigraphic methods available which are of potential practical use in the assessment of malignant breast disease as well as looking at the possible role of nuclear medicine in the treatment of advanced disease.

Journal Article↗
PubMed2001

6-oxo-PGF(1 alpha)and 8-epi-PGF(2 alpha)in the arterial wall layers of various species: a comparison between intact and atherosclerotic areas.

PGI(2)and 8-epi-prostaglandin(PG)F(2 alpha)are antagonizing compounds. For both a key role in vascular pathology has been hypothesized. The isoprostane 8-epi-PGF(2 alpha)and the stable derivative of PGI(2), 6-oxo-PGF(1 alpha)were determined immunologically in the arterial wall of various species including humans. Human arterial tissue contained the highest amounts of 8-epi-PGF(2 alpha)and synthesized the lowest PGI(2). A significant negative correlation between 8-epi-PGF(2 alpha)and 6-oxo-PGF(1 alpha)was observed. Atherosclerotic segments showed significantly higher 8-epi-PGF(2 alpha)and lower 6-oxo-PGF(1 alpha). 8-epi-PGF(2 alpha)in the intima was higher than in the media, the highest amounts being found in foam-cell rich areas. Synthetic (activated) smooth muscle cells were associated with an enhanced 8-epi-PGF(2 alpha)as well as 6-oxo-PGF(1 alpha). Tissue samples derived from smokers contained more 8-epi-PGF(2 alpha)and produced less PGI(2). The by far highest 8-epi-PGF(2 alpha)/6-oxo-PGF(1 alpha)ratio was found in foam cell rich areas. Similar findings were obtained in rabbit and in minipig arteries. The total 8-epi-PGF(2 alpha)/6-oxo-PGF(1 alpha)ratio is low in normal tissue, increases significantly in an active atherosclerotic process and seems to be even further increased in an inactive atherosclerotic process. These findings are providing an information on the extent of oxidation injury at various sites of different types of atherosclerotic process.

6-Ketoprostaglandin F1 alpha↗
PubMed2001

Do human platelets express COX-2?

The rate-limiting enzyme in prostaglandin (PG)- and thromboxane (TX)-synthesis is known as cyclooxygenase (COX). The COX-enzyme family consists of the classical COX-1 and the inducible COX-2-enzyme. To investigate whether platelets contain COX-2, we measured thiobarbituric acid reactive substances (TBARS) after either blocking COX-1 or COX-2 or adding compounds known to affect COX-expression. To stimulate platelets' different reagents such as collagen, thrombin and arachidonic acid (AA) were used. The inhibitors used in this study were acetylsalicylic acid (ASA), indomethacin and NS-398. Using the western-blot technique, we failed to detect COX-2 in platelets while COX-1 was detectable. We were not able to discover COX-2 in platelets using the methods we applied. As the amount of COX-2 in platelets might be below the detection limit of the methods used, the biological relevance COX-2 in platelets, if even existing at low amounts, remains to be established.

Adult↗
PubMed2001

Increase of isoprostane 8-epi-PGF(2alpha)after restarting smoking.

Isoprostanes are known as reliable markers of in vivo oxidation injury. Cigarette smoking has been shown to be associated with a significant increase in 8-epi-PGF(2alpha), a major member of this family of compounds. Quitting smoking reduces 8-epi-PGF(2alpha) values to normal within a couple of weeks only. In this follow-up we checked the 8-epi-PGF(2alpha), values in plasma, serum and urine in 28 people who restarted smoking after a quitting attempt of various duration. 8-epi-PGF(2alpha)shows a certain increase after restarting smoking reaching a maximum after already 1 week. Continuation of smoking does not significantly further increase 8-epi-PGF(2alpha). These data indicate a fast response of restarting as on quitting smoking on in vivo oxidation injury. The oxidation injury reflected by 8-epi-PGF(2alpha)may be a key pathogenetic mechanism in smoking-induced vascular injury.

Adult↗
PubMed2001

Regular ingestion of opuntia robusta lowers oxidation injury.

The influence of opuntia robusta (prickly pear), a traditionally used dietary nutrient against diabetes mellitus among the American Indian population, was examined in 15 young patients suffering from familial heterozygous isolated hypercholesterolemia. Oxidation injury was determined via 8-epi-PGF(2 alpha)in plasma, serum and urine. Daily consumption of 250 g broiled edible pulp of prickly pear had no influence on body weight and body fat composition. Total cholesterol was lowered (P<0.01) as was LDL-cholesterol (P<0.04). No significant changes were observed either in triglycerides or in HDL. Prickly pear induced a significant decrease in plasma (27.9+/-3.3-->25.6+/-3.2;P<0.03), serum (302.0+/-11.4-->283.2+/-14.5;P<0.0003) and urinary (355.9+/-18.4-->323.9+/-16;P<0.00002) 8-epi-PGF(2alpha)values. The findings on a decrease of 8-epi-PGF(2alpha)were more pronounced in females than in males, the highest significance being found in urine, while, in contrast, the effects on total- and LDL-cholesterol were more pronounced in males. A prerunning 4 weeks period of dietary counseling had no significant effect on either of the parameters examined. These findings indicate that the regular ingestion of opuntia robusta is able to significantly reduce in-vivo oxidation injury in a group of patients suffering from familial hypercholesterolemia. This traditional food of the American Indians thus may have a significant cardiovascular benefit.

Adult↗
PubMed2001

Radiation exposure from patients treated with 165Dy-ferric hydroxide.

In radiation synovectomy about 10 GBq 165Dy-ferric hydroxide is injected into major joints. Measurements of the dose rates were performed at distances of 5 cm, 0.5 m, 1 m and 2 m from the surface of the treated joints (knees) until 200 min after the application in 16 patients in order to estimate the radiation exposure of persons in the neighbourhood of the patients. The highest doses were estimated for the fingers of the technologist (320 microSv) and for the physician (700 microSv). Special shields for the syringes were constructed for dose reduction. The whole-body doses were 103 microSv for the technologist and 40 microSv for the physician. After the discharge of the patient to a ward or home, other persons at 1 m distance from the patient might receive 88 microSv, which is less than 9% of the annual permissible dose. Our results clearly demonstrate that the calculated radiation exposure to personnel and family members is well below the maximum annual dose limit for non-professionally exposed persons.

Algorithms↗
PubMed2001

In vitro adsorption of 99Tc(m)-MIBI, 99Tc(m)-tetrofosmin, 99Tc(m)-furifosmin and 99Tc(m)O4- onto tubes.

Adsorption of radiopharmaceuticals onto disposable syringes has been reported to amount to levels of almost 50%. Data on adsorption of radiopharmaceuticals onto materials used for in vitro studies are extremely limited. We assessed the extent of adsorption of 99Tc(m) hexakis(2-methoxyisobutylisonitrile) (99Tc(m)-MIBI), 99Tc(m)-tetrofosmin, 99Tc(m)-furifosmin and 99Tc(m)O4 onto tubes used for in vitro measurement of cellular uptake of these radiopharmaceuticals. The influence on adsorption of different incubation media, temperature and time of incubation was evaluated. Total (not corrected for adsorption) uptake was compared with corrected, net cellular uptake in SK-BR-3, MCF-7 and liposarcoma cell lines. Values of adsorption ranging from 0.94+/-0.13% to 7.07+/-0.46% were found. The extent of adsorption of all the radiopharmaceuticals varied with the type of incubation medium and the incubation temperature. With 99Tc(m)-furifosmin, adsorption was dependent on the incubation time as well on the incubation temperature and some of the incubation media investigated. Our findings indicate that systematic investigations to evaluate the adsorption of radiopharmaceuticals onto materials used during in vitro studies of cellular uptake should be considered a mandatory aspect of quality control.

Adsorption↗
PubMed2001

Statin induced myopathy does not show up in MIBI scintigraphy.

Statin induced myopathy is the most commonly seen side effect in users of this family of drugs. Their different forms present with either creatine phosphokinase (CK) elevation or not, signs of in vivo oxidation injury or not or a combination of both. The pathogenetic background, however, still remains obscure. As MIBI, beside myocardial and tumour scintigraphy, is useful in detecting muscle metabolic abnormalities, an increased uptake of MIBI in the diseased muscular segments could be expected. We investigated seven patients (five males, two females; aged 36-56 years) with statin induced myopathy with either elevated CK, isoprostanes or muscle pains at varying combinations. MIBI whole-body imaging was done immediately, the patients still being on the respective statin. Sixteen patients (six males, 10 females) suffering from lung or breast cancer and being on statins served as controls. No uptake abnormalities in any muscular segment either in the patients or the control group were seen. Thus, MIBI scintigraphy is not useful, apparently, in diagnosing and eventually localizing statin induced myopathy. These findings indicate that MIBI scintigraphy is of no help for diagnosis and gaining further insight into statin induced myopathy.

Adult↗
PubMed2001

Verapamil decreases accumulation of 99Tcm-MIBI and 99Tcm-tetrofosmin in human breast cancer and soft tissue sarcoma cell lines.

99Tcm-methoxyisobutylisonitrile (99Tcm-MIBI) and 99Tcm-tetrofosmin are cationic tracers recognized by the efflux pump P-glycoprotein (Pgp). Verapamil has been shown to be a competitive inhibitor of Pgp, and was one of the first multidrug-resistant reversing agents identified. The aim of this preclinical in vitro study was to evaluate the effects of verapamil on the accumulation of 99Tcm-MIBI and 99Tcm-tetrofosmin in the human breast cancer cell lines MCF-7 and SK-BR-3 and in the human soft tissue sarcoma cell lines SW 982 and SW 1353, in comparison with respective control cells, i.e. without preincubation with verapamil. After preincubation with 10 or 100 microM of verapamil for 15 or 30 min, the 99Tcm-MIBI and 99Tcm-tetrofosmin accumulation in cells was assessed at 10, 30 and 60 min after incubation with these tracers. Addition of verapamil caused a decline in the accumulation of the two tracers at all incubation times, as compared with control cells. These effects of verapamil were neither dose- nor preincubation time-dependent in most cells. Our data indicate that verapamil is not a promising agent for increasing the sensitivity of scintigraphy with 99Tcm-MIBI or 99Tcm-tetrofosmin, or for evaluating Pgp tumour status in these types of tumours.

Adenocarcinoma↗