A. Oguogho

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.

The isoprostane, 8-epi-PGF2α, 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.

Isoprostane 8-epi-PGF2α 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.

Maternal cigarette smoking increases F2-isoprostanes and reduces prostacyclin and nitric oxide in umbilical vessels

The objective of this study was to evaluate the influence of smoking on F2-isoprostanes, prostacylin and nitric oxide in human umbilical vessels. Umbilical cords from 13 babies of smoking mothers and from 28 babies of non-smoking mothers were examined for levels of F2-isoprostanes, prostacyclin, L-arginine, and L-citrulline. Forty-one umbilical arteries and eleven umbilical veins were analyzed. Statistical analysis of data was done using modified t-test. Cigarette smoking increased F2-isoprostane levels and reduced the generation of prostacyclin, L-arginine and L-citrulline comparably in umbilical arteries and veins. Notably, in umbilical cords of babies of non-smoking mothers the F2-isoprostane level was significantly higher in arteries. Cigarette smoking correlates with a direct vasoconstrictive effect. We suggest that smoking might enhance the vasoconstrictory capacity in umbilical arteries by increased F2-isoprostanes and by a simultaneous decrease in the production of the vasodilatory compounds, prostacyclin, and nitric oxide.

Daily prickly pear consumption improves platelet function

Prickly pear is traditionally used by Pima Indians as a dietary nutrient against diabetes mellitus. We examined the effect of daily consumption of 250 g in 8 healthy volunteers and 8 patients with mild familial heterozygous hypercholesterolemia on various parameters of platelet function. Beside its action on lipids and lipoproteins, prickly pear consumption significantly reduced the platelet proteins (platelet factor 4 and beta-thromboglobulin), ADP-induced platelet aggregation and improved platelet sensitivity (against PGI2 and PGE1) in volunteers as well as in patients. Also plasma 11-DH-TXB2 and the WU-test showed a significant improvement in both patients and volunteers. In contrast, collagen-induced platelet aggregation and the number of circulating endothelial cells showed a significant response in patients only. No influence of prickly pear ingestion on peripheral platelet count was monitored. The dietary run-in period did not influence any of the parameters of haemostasis examined. No sex difference was seen. Prickly pear may induce at least part of its beneficial actions on the cardiovascular system via decreasing platelet activity and thereby improving haemostatic balance.

Isoprostanes quickly normalize after quitting cigarette smoking in healthy adults.

Background: Isoprostanes and in particular 8-epi-PGF2alpha have been claimed as a useful measure for in-vivo oxidation injury. While smokers show elevated 8-epi-PGF2alpha, the behaviour during quitting smoking is unknown. Methods and results: We determined 8-epi-PGF2alpha 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-PGF2alpha shows a rapid decline within a few days almost completely normalizing within 4 weeks. Conclusion: The cigarette-smoking associated in-vivo oxidation injury almost completely disappears within 4 weeks of quitting smoking.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.

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.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 × 6 h × 5 d × 4 wk; group B [n = 9]; 60 mug PGE1/2 h × 5 d × 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...

VARIABLE INFLUENCE OF STATINS ON ISOPROSTANES IN HYPERLIPIDEMIA

Although statin therapy under normal circumstances reduces oxidation injury, the isoprostane 8-epi-PGF2α may increase various time intervals after initiation of treatment in certain patients for unknown reason. All statins seem to be equally affected. Stopping statin therapy causes reversal within about 2 weeks. During and after exercise the 8-epi-PGF2α increase is more frequent. Isoprostanes may become relevant to discover a statin side effect. The pathophysiological and clinical consequences of this finding need to be elaborated.

Increased Isoprostanes in Children of Smoking Parents

Experimental tobacco smoking (ETS) is attracting increasing attention [1] as a potential risk factor for the development of atherosclerosis [[2],[3]]. Assessment of ETS under real life conditions of biochemical changes is difficult. We therefore assessed the isoprostane 8-epi-PGF2α in children of parents diagnosed for familial hyperlipoproteinemia at the receptor level with the aim to clarify whether parental smoking may have an influence.

Evidence for Enhanced Oxidative Stress in Coronary Heart Disease and Chronic Heart Failure

Oxidation injury has been claimed as one of the key factors in the development of coronary heart disease and chronic heart failure [1,2]. The isoprostane 8-epi-PGF22α is gaining increasing interest as reliable marker of in-vivo oxidation injury [3]. As it causes among others coronary vasoconstriction [4] its pathophysiological role may become even more important. We therefore assessed the isoprostane 8-epi-PGF2α in arteries, veins, heart valves and myocardial tissue immunochemically as well as by immunohistochemistry. Furthermore, 8-epi-PGF2α was determined in plasma and urine of patients with CHD compared to patients with dilated and ischemic CMP.