(Iso) Prostaglandins in saliva indicate oxidation injury after radioiodine therapy.

UNLABELLED: As salivary glands concentrate radioiodine the radiation injury associated with 131I-therapy may result in sialoadenitis and xerostoma leading to a lasting impaired quality of life. Recently we reported about prostaglandin concentration changes as biochemical markers for radiation injury. Isoprostanes, a new family of prostaglandin-like compounds, have been demonstrated to be reliable markers for oxidation injury in vivo. PATIENTS AND METHODS: In this study we examined the levels of 8-epi-PGF2alpha, the major member of the isoprostane family in 24 patients undergoing 1311 treatment in different doses for hyperthyroidism and differentiated thyroid cancer. 6 healthy sex and age-matched volunteers were monitored in parallel. Saliva(iso)prostaglandins were determined before 131I treatment, as well as 1, 3, 7, 14, 21, and 28 days, and 2, 3, and 6 months after therapy. RESULTS: 8-epi-PGF2alpha showed a significant 1311 dose-dependent temporary increase. The alterations were comparable in all investigated patients and significantly higher in cigarette smokers. TXB2 and 6-oxo-PGF, showed a dose-dependent increase too. TXB2 was higher in cigarette smokers and 6-oxo-PGF1alpha lower as compared to non-smokers. CONCLUSION: These results clearly demonstrate a dose- and time-dependent tissue (TXB2, 6-oxo-PGF1alpha) and oxidation in-jury (8-epi-PGF2alpha) after 131I-therapy in the salivary glands.

(Iso) Prostaglandins in saliva indicate oxidation injury after radioiodine therapy / (Iso) Prostaglandinas en saliva indican daño oxidativo después de terapia con radioyodo

As salivary glands concentrate radioiodine the radiation injury associated with 131I-therapy may result in sialoadenitis and xerostoma leading to a lasting impaired quality of life. Recently we reported about prostaglandin concentration changes as biochemical markers for radiation injury. Isoprostanes, a new family of prostaglandin-like compounds, have been demonstrated to be reliable markers for oxidation injury in vivo. Patients and methods: In this study we examined the levels of 8-epi-PGF2, the major member of the isoprostane family in 24 patients undergoing 131I treatment in different doses for hyperthyroidism and differentiated thyroid cancer. 6 healthy sex and age-matched volunteers were monitored in parallel. Saliva (iso)prostaglandins were determined before 131I treatment, as well as 1, 3, 7, 14, 21, and 28 days, and 2, 3, and 6 months after therapy. Results: 8-epi-PGF2 showed a significant 131I dose-dependent temporary increase. The alterations were comparable in all investigated patients and significantly higher in cigarette smokers. TXB2 and 6-oxo-PGF1 showed a dose-dependent increase too. TXB2 was higher in cigarette smokers and 6-oxo-PGF1 lower as compared to non-smokers. Conclusion: These results clearly demonstrate a dose- an time-dependent tissue (TXB2, 6-oxo-PGF1) and oxidation injury (8-epi-PGF2) after 131I-therapy in the salivary glands (AU)

Ya que las glándulas salivares concentran radioyodo, el daño de la radiación asociado a la terapia con 131I puede dar lugar a sialoadenitis y xerostoma, conduciendo a una calidad de vida dañada de forma duradera. Recientemente, hemos informado sobre cambios en la concentración de prostaglandina como marcadores bioquímicos para daño después de radiación. Se ha demostrado que los isoprostanos, una nueva familia del compuestos del tipo prostaglandina, son marcadores fiables para daño oxidativo in vivo. Pacientes y métodos: En este estudio, exploramos los niveles de 8-epi-PGF2, el miembro más importante de la familia de isoprostanos, en 24 pacientes recibiendo tratamiento 131I con dosis diferentes para hipertiroidismo y cáncer de tiroides diferenciados. Fueron monitorizados en paralelo 6 voluntarios sanos pareados por edad y sexo. Se determinaron (iso) prostaglandinas en saliva antes del tratamiento de 131I, así como 1, 3, 7, 14, 21 y 28 días y 2, 3, y 6 meses después del tratamiento. Resultados: 8-epi-PGF2 demostraron un aumento temporal significativo dependiendo de la dosis de 131I. Las alteraciones en todos los pacientes investigados fueron comparables y significativamente más altas en los que fumaban. TXB2 y 6-oxo-PGF1 demostraron también un aumento dependiente de la dosis. TXB2 fue más alto en los que fumaban y 6-oxo-PGF1 más bajo al compararlo con no-fumadores. Conclusión: Estos resultados demostraron claramente un daño tisular tiempo y dosis dependiente (TXB2, 6-oxo-PGF1) y daño oxidativo (8-epi-PGF2) después de terapia con 131I en las glándulas salivares (AU)

Effect of giving up cigarette smoking and restarting in patients with clinically manifested atherosclerosis.

Cigarette smoking, a key risk factor for the development of vascular disease, is associated with an increased 8-epi-prostaglandin (PG) F(2alpha). Elevated 8-epi-PGF(2alpha) has been found in vascular tissue, blood and urine as well. We examined the influence of quitting cigarette smoking in 71 patients (38 males, 33 females; aged 32-67 a) with clinically manifested atherosclerosis and various risk factors. In addition, in eight patients with hypercholesterolemia without clinical manifestation of atherosclerosis quitting smoking was monitored as well. Twenty-six of the patients with manifested atherosclerosis and five with hypercholesterolemia restarted and the isoprostanes in plasma, serum and urine were monitored in these patients as well. Quitting cigarette smoking induces an immediate decline becoming significant after 1 or 2 weeks. Restarting smoking results in an increase in 8-epi-PGF(2alpha) reaching prevalues within almost 1 week. These findings indicate that the in vivo oxidation injury associated with cigarette smoking quickly decreases after quitting but increases soon after restarting immediately.

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.

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.

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.

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.

[Unaltered homocysteine levels during simvastatin therapy]. / Unverändertes Homocystein unter Simvastatin-Therapie.

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.

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.

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.

Comparative (99m)Tc-MIBI, (99m)Tc-tetrofosmin and (99m)Tc-furifosmin uptake in human soft tissue sarcoma cell lines.

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

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.

Technetium-99m-tetrofosmin: a new agent for melanoma imaging?

The aim of our study was to examine whether technetium-99m 1,2-bis[bis(2-ethoxyethyl) phosphino]ethane (tetrofosmin) a lipophilic, cationic tracer which was first developed for myocardial perfusion imaging, could be a new radiopharmaceutical for melanoma imaging. We therefore used two human cell lines, SK-MEL 28 and 5i8 A2 (n = 6, cell concentration 106/ml, incubation at 22 degrees C and 37 degrees C, 50-100 approximately lCi/ml Tc-99m-tetrofosmin, time of incubation 10-180 minutes). The cellular uptake by both cell lines was determined. In contrast to another non- melanoma tumor cell line MCF-7 (a human adenocarcinoma breast cancer) which reached steadystate almost immediately (within 10 minutes), the cellular uptake of SK-MEL-28 increased after 60 minutes and showed a very high uptake (> 10%) after 120 minutes and decreased after 180 minutes (6-8%), while the uptake in 518 A2 cells was about 5% after 90 minutes. Our data show that Tc-99m-tetrofosmin could be a promising agent for melanoma imaging.