Persistently elevated CKMB and negative troponin T in a patient at ischaemic risk with chest pain.

Analytical interference in laboratory assays is not only unpredictable but also an underestimated problem. Not recognising these interferences can lead to misdiagnosis and mismanagement of patients. We present a case of a patient with chest pain and ischaemic risk factors with incongruent biochemical results. These results were discovered to be due to the presence of macro-creatine kinase (macro-CK) in vivo interfering with the CKMB activity assay.

Dietary iron elevates LDL-cholesterol and decreases plasma antioxidant levels: influence of antioxidants.

High body iron and LDL-cholesterol concentrations, and antioxidant deficiency, are regarded as risk factors for ischemic heart disease. Iron is well known for causing oxidative damage and antioxidants for their beneficial effects on radical scavenging. It is, however, unknown whether or not dietary iron causes depletion of plasma antioxidants; causes lipid peroxidation; alters HDL- and LDL-cholesterol, and triglyceride concentrations. Rats received diets differing only in iron concentration--15 mg/Kg, 35 mg/Kg, 150 mg/Kg or 300 mg/Kg diet. The second group of rats received antioxidants (alpha-tocopherol and beta-carotene) in their drinking water. Increasing dietary iron increased plasma lipid hydroperoxide and LDL-cholesterol concentrations, but did not affect HDL-cholesterol or triglyceride concentrations. It decreased antioxidants, alpha-tocopherol and retinol. Antioxidant supplementation inhibited the above changes.

Dietary iron concentration alters LDL oxidatively. The effect of antioxidants.

Low-density lipoprotein (LDL) cholesterol participates in the atherosclerotic process only after oxidative modification (o-LDL). Persons with elevated body iron concentrations are at higher risk of atherosclerosis. Iron in vitro is capable of oxidizing LDL, but it is unknown whether or not high dietary iron concentrations alter LDL in vivo. The aim of this study was, therefore, to investigate (i) whether dietary iron concentrations cause LDL-cholesterol oxidation and (ii) whether antioxidants can prevent such changes. Rats received diets differing only in iron concentration: 35 mg/kg, 150 mg/kg or 300 mg/kg diet. A LDL-VLDL particle was isolated and the following parameters measured: malondialdehyde and lipid hydroperoxide concentrations (as an indication for lipid peroxidation); alpha-tocopherol and retinol concentrations (as antioxidants); protein sulfhydryl and carbonyl concentrations (as an indication of protein modification); agarose gel electrophoresis and cholesterol/protein ratio. Dietary iron increased LDL-VLDL lipid peroxidation (malondialdehyde and lipid hydroperoxide concentrations), protein modification (sulfhydryl concentration), agarose migration distance and band width as well as cholesterol/protein ratio. Increased quantities of dietary iron led to a higher degree of oxidative change in LDL-VLDL. Lipid peroxidation, as well as protein modification, occurred, suggesting apoB changes. This was probably due to diminished antioxidant concentrations of alpha-tocopherol and beta-carotene. Antioxidant supplementation (alpha-tocopherol and beta-carotene), however, prevented all the above changes and could be helpful in the prevention of atherosclerosis.

Dietary iron alters liver, erythrocyte and plasma antioxidant and nitrite levels, and also sensitizes the heart to ischemia/reperfusion.

The aim of the study was to determine whether dietary iron within the normal range is (i) responsible for oxidative changes in the liver, erythrocytes and plasma; and (ii) make the heart more susceptible to ischemia/reperfusion injury. Female rats were allocated to four groups according to diet supplemented with either 15, 35, 150, or 300 mg iron/kg diet. After 4 months the following statistical difference in the two higher dietary groups were observed compared to the lower ones: (i) decreased antioxidant concentrations in liver, plasma and erythrocytes (alpha-tocopherol and ascorbic acid); (ii) increased plasma nitrite concentration; (iii) ischemia/reperfusion elevated LMWI and MDA concentrations and decreased ascorbate concentrations. This study clearly showed that increased dietary iron concentration causes oxidative changes in plasma, erythrocytes and liver. Higher dietary iron aggravated the outcome of ischemia/reperfusion injury as indicated by an elevated malondialdehyde concentration in the two higher dietary iron groups.

Influence of ferritin levels on LDL cholesterol concentration in women.

Various researchers have observed a higher risk for atherosclerosis when body iron concentration is elevated. The exact mechanism, however, is not known, but probably occurs catalytically via iron. Whether or not body iron concentration has an effect on plasma lipoproteins is also unknown. The aim of this study was to investigate whether or not ferritin concentration within the normal range correlate with LDL-cholesterol (an atherosclerotic risk factor), HDL-cholesterol, apoB, triglyceride and the mobility of LDL particles. Blood was drawn from healthy female volunteers and the above parameters measured. LDL-cholesterol, apoB and the electrophoretic mobility of LDL particles were elevated with increasing ferritin concentrations. Both modified or oxidized LDL and elevated LDL concentration are regarded as risks for atherosclerosis and ischemic heart disease, suggesting that higher body iron is important in this process.

The in vivo effect of different bedding materials on the antioxidant levels of rat heart, lung and liver tissue.

Several experimental effects due to wood-derived bedding have been reported. Female Sprague Dawley rats were kept on pine shavings, eucalyptus pulp, vermiculite and in wire-bottomed cages without bedding for 14 days whereafter normal values for the antioxidants ascorbic acid and reduced glutathione (G-SH) in rat heart lung and liver tissue were determined and compared. Statistically significant differences were observed for lung G-SH between pine shavings and eucalyptus pulp (p < 0.0183), and heart G-SH between vermiculite and eucalyptus pulp (p < 0.0948). The highest levels of liver G-SH were obtained using pine shavings compared to vermiculite (p < 0.0001), eucalyptus pulp (p < 0.0002) and wire floor (p < 0.0001). Statistically significant differences in ascorbic acid concentrations could only be described between the wire-bottomed cages and eucalyptus pulp (p < 0.0333) for lung tissue and between pine shavings and eucalyptus pulp for liver tissue (p < 0.042). Although no statistically significant differences were observed in heart ascorbic acid levels between the different bedding applications, the concentration obtained using vermiculite was approximately 50% higher than that observed with the other materials. Pine shavings, eucalyptus pulp and wire floors demonstrated virtually the same heart tissue ascorbic acid levels. It was thus demonstrated that bedding material can alter the tissue antioxidant concentration of laboratory animals, limiting the comparison of this type of result between institutions to those using identical environmental conditions.

Effect of flavonoids on the outcome of myocardial mitochondrial ischemia/reperfusion injury.

There is evidence that flavonoid intake correlates inversely with coronary heart disease risk. Flavonoids are widely distributed in food and drinks and act as antioxidants and iron chelators. The aim of this study was to determine whether pycnogenol (a flavonoid extracted from the bark of Pinus pinaster) and catechin could minimise the myocardial mitochondrial damage due to ischemia/reperfusion. Using the rat heart model of ischemia/reperfusion we found that pycnogenol had no significant effect on the resultant damage, while catechin suppressed the observed elevation of low molecular weight iron during ischemia/reperfusion which might explain the significantly reduced mitochondrial injury when using catechin in the perfusate. Our results suggest that some flavonoids might be effective in minimizing ischaemic/reperfusion injury and would require further detailed investigation.

Ischemia/reperfusion injury is aggravated by an iron supplemented diet and is partly prevented by simultaneous antioxidant supplementation.

In humans high levels of storage iron as well as low iron binding capacity are considered risks for ischemic heart disease development. The aim of this study was to determine whether a diet containing iron to a concentration of the recommended upper limit alters the degree of myocardial ischemic/reperfusion injury on rats and whether simultaneous antioxidant supplementation had any effect. Results indicate that the iron supplemented diet increased the degree of oxidative injury while simultaneous antioxidant supplementation prevented much of this increase. The mechanism for this was probably an elevated hydroxyl radical production due to the enlarged transit iron pool.

Salicylate in the perfusate during ischemia/reperfusion prevented mitochondrial injury.

Salicylate is widely used as a stable trap for the highly reactive hydroxyl radical. The purpose of this study was to determine whether the addition of salicylate to hearts subjected to ischemia and reperfusion was able to prevent some injury. Salicylate was able to inhibit mitochondrial damage, and preserved ascorbate and alpha-tocopherol depletion due to ischemia/reperfusion in rat hearts. It did not prevent the elevation of low molecular weight iron. We conclude that salicylate functions as an antioxidant and afforded protection against ischemia and reperfusion.

Antioxidant supplementation partially protects against myocardial mitochondrial ischemia/reperfusion injury, but ascorbate in the perfusate prevented the beneficial effect.

This study was undertaken to investigate whether prior antioxidant supplementation had a beneficial effect on subsequent myocardial ischemic/reperfusion injury and whether addition of ascorbate during ischemia/reperfusion had any effect. Supplementation with antioxidants resulted in elevated concentrations of myocardial alpha-tocopherol, but not of ascorbate. Combined supplementation with alpha-tocopherol, beta-carotene and ascorbic acid gave the highest myocardial alpha-tocopherol concentration. Hearts of rats supplemented with antioxidants was partially protected to ischemia/reperfusion as indicated by the mitochondrial function. However, addition of ascorbate during ischemia/reperfusion nullified this protective effect.

Processing novel compounds: evidence for interactive meaning activation of ambiguous nouns.

In three experiments, the meaning activation of ambiguous nouns in novel nominal compounds was investigated. Ambiguous nouns were unbalanced homographs occurring as the second members of the compound. Meaningful interpretations of the compounds were based on either the dominant or the subordinate meaning of the ambiguous noun. In Experiment 1, visually presented novel compounds serving as primes were followed at varying intervals by targets associatively related to distinct meanings of the ambiguous noun. In a lexical decision task, facilitation effects were found only for targets related to the meaning that was relevant for the interpretation of the compound. Experiment 2 showed that interactive activation could not be attributed to differences in semantic relatedness between the first members of compounds and targets. Experiment 3 demonstrated equal intralexical relatedness between members for both types of compounds. It is proposed that interactive activation may facilitate the interpretation of the novel compound. Compatible meaning aspects of the nouns may become more strongly activated, and incompatible meaning aspects may not become activated. The selection of meaning aspects relevant for interpretation would thereby be simplified.

Exposure of rats to low concentration of cigarette smoke increases myocardial sensitivity to ischaemia/reperfusion.

It is suggested that passive smoking or smoke-exposure increase the risk of coronary heart disease. The same mechanisms as active smoking might play a role. The aim of this study was to determine whether exposure to smoke aggravated ischaemia/reperfusion injury. As a parameter of cellular function and integrity mitochondrial oxidative function was measured. Low molecular weight iron (LMWI) and alpha-tocopherol levels were determined to assess the possibility of toxic hydroxyl radical involvement in myocardial ischaemia/reperfusion injury of smoke-exposed rats. Rats were exposed to a small concentration of cigarette smoke for 2 months (the carboxyhemoglobin concentration did not increase), whereafter hearts were isolated and subjected to ischaemia and ischaemia followed by reperfusion. Mitochondrial oxidative function, low molecular weight iron and alpha-tocopherol were determined. The impairment in mitochondrial oxidative function, LMWI content elevation and the decrease in alpha-tocopherol concentration during ischaemia/reperfusion were significantly more severe in hearts of smoke-exposed rats than non-smokers. These results suggest that exposure to smoke increased the sensitivity of hearts to ischaemia/reperfusion injury, and that a free radical mechanism might participate.

The protective effect of desferal on rat myocardial mitochondria is not prolonged after withdrawal of desferal.

Reperfusion of ischaemic myocardium is necessary to sustain tissue viability (without it the tissue becomes necrotic), but reperfusion, on the other hand, can damage cells which have survived ischaemia. There is now considerable evidence that oxygen radicals, especially hydroxyl radicals produced via the Haber-Weiss and Fenton reactions, are responsible for reperfusion damage. Various investigators have reported that desferal, an iron chelator, has a beneficial effect on the myocardium during ischaemia and reperfusion. The aim of this study was two-fold: i) whether superoxide anions in the absence of LMWI can impair mitochondrial function, and ii) whether the protective effect of desferal on the mitochondrial function persists after withdrawal of desferal. Experiments were done on isolated rat hearts subjected to normothermic ischaemic cardiac arrest (NICA), with or without desferal, followed by 15-min reperfusion with desferal, followed by 15-min perfusion without desferal, or a hypoxanthine/xanthine oxidase medium that generates superoxide anions (with or without desferrioxamine (desferal) in the perfusate). Mitochondrial function (QO2 (state 3), ADP/O and OPR) as well as LMWI were measured. Our results indicated that i) superoxide anions and/or hydrogen peroxide can, independently of LMWI, damage the mitochondria, and ii) withdrawal of desferal after the respiratory burst resulted in the same or more severe mitochondrial damage than without any desferal.

Antioxidant vitamin supplementation of smoke-exposed rats partially protects against myocardial ischaemic/reperfusion injury.

Our previous studies showed that exposure of rats to limited periods of cigarette smoke resulted in more severe myocardial damage when their hearts were subjected to myocardial ischaemia/reperfusion. The aim of this study was to determine whether supplementation of rats with antioxidant vitamins alpha-tocopherol and beta-carotene was able to protect their hearts against the increase in ischaemia/reperfusion injury caused by smoke-exposure. The parameters measured were mitochondrial oxidative function, cellular levels of alpha-tocopherol and low molecular weight iron (LMWI). Supplementation with antioxidant vitamins resulted in significantly less mitochondrial functional oxidative damage compared to that observed in the controls. Supplementation did not affect the cellular LMWI content, suggesting that the generation rate of hydroxyl radicals was similar in both groups. The protective effect of alpha-tocopherol and beta-carotene supplementation on the mitochondrial function against ischaemia/reperfusion could be due to their free radical scavenging action. Supplementation with antioxidant vitamins, therefore, had a beneficial effect on the excessive myocardial ischaemia/reperfusion injury of smoke exposed rats.

The interpretation of isolated novel nominal compounds.

The lexical decision task was used to investigate interpretative processing of isolated novel compounds (noun-noun nominals). On the basis of interpretability ratings, novel compounds were classified as being of either high or low interpretability. In a lexical decision task in which novel compounds functioned as nonwords, a significant interference effect was found for compounds of high interpretability. In a naming task, no differences were found between the two types of novel compounds, but lexicalized compounds resulted in shorter latencies than did novel compounds. Novel compounds were also shown to be interpreted under conditions unfavorable to morphological decomposition, suggesting that the interpretation process is beyond strategic control by the subject. Equal semantic priming effects were obtained for members of established semantic categories and nouns of highly interpretable compounds. Interpretative processes dealing with a limited set of basic semantic relations and analogy with lexicalized compounds are discussed.

Effect of various mixtures of diethylether, halothane, nitrous oxide and oxygen on low molecular weight iron content and mitochondrial function of the rat myocardium.

Anaesthetic drugs can induce reversible as well as irreversible changes in cell membranes and intracellular proteins as well as lipid peroxidation in the liver. Low molecular weight iron species (LMWI) can by their catalytic activity contribute to the generation of free radicals (hydroxyl radicals). Free radicals are a recognisable cause of intracellular damage. Impaired mitochondrial function is also a sign of intracellular damage, which is usually irreversible. Thus, an agent may be cytotoxic when it causes a significant increase in intracellular LMWI. Whether the LMWI arise from ferritin or is released from iron containing proteins, the same reaction occurs. As long as LMWI can undergo redox cycling, hydroxyl radicals can be formed. We investigated the effect of various mixtures of diethylether, halothane, nitrous oxide and oxygen on the intracellular LMWI content and mitochondrial function of the rat myocardium. Hearts isolated from rats anaesthetised with diethylether showed an increase in the cytosolic LMWI compared to the control group. No increase in mitochondrial LMWI was demonstrated. Subsequent perfusion of the isolated hearts showed a further increase in the LMWI. On perfusion the mitochondrial LMWI increased in comparison with controls. Mitochondrial function was significantly impaired as measured by the QO2 (state 3), ADP/O ratio and oxidative phosphorylation rate (OPR). Exposure of rats to 50% nitrous oxide for 15 minutes increased the myocardial LMWI, but had no effect on mitochondrial function. Exposure to room air for 30 minutes before isolating the hearts, still showed a significant increase in LMWI with no detectable change in mitochondrial function.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of desferal on rat heart mitochondrial function, iron content, and xanthine dehydrogenase/oxidase conversion during ischemia-reperfusion.

Cardiac mitochondrial function as measured by oxidative phosphorylation is impaired by ischemia; and, this deteriorates even further on reperfusion of the heart. Free oxygen radicals, especially the formation of hydroxyl radicals via the iron-catalyzed Haber-Weiss and Fenton reactions have been implicated in the reperfusion injury. In this study, the effect of desferrioxamine (desferal) in the perfusate on mitochondrial function of isolated rat hearts during different periods of normothermic ischemic cardiac arrest (NICA), and subsequent reperfusion was investigated. Mitochondrial functions measured were the QO2 (state 3); ADP/O ratio and oxidative phosphorylation; the mitochondrial, loosely bound (chelateable) iron (LB-iron); the xanthine dehydrogenase and xanthine oxidase activities. Inclusion of desferal in the perfusion solution significantly improved mitochondrial function during the different NICA periods, and prevented the deterioration of mitochondrial function resulting from reperfusion. Desferal did not significantly affect the LB-iron content of the mitochondria or the ratio of xanthine dehydrogenase/xanthine oxidase activities in the mitochondria during NICA or reperfusion. Our experiments suggest that iron, which is free to be chelated by desferal, plays a role in this injury to the rat myocardium.

Stiffness and hysteresis properties of some prosthetic feet.

A prosthetic foot is an important element of a prosthesis, although it is not always fully recognized that the properties of the foot, along with the prosthetic knee joint and the socket, are in part responsible for the stability and metabolic energy cost during walking. The stiffness and the hysteresis, which are the topics of this paper, are not properly prescribed, but could be adapted to improve the prosthetic walking performance. The shape is strongly related to the cosmetic appearance and so can not be altered to effect these improvements. Because detailed comparable data on foot stiffness and hysteresis, which are necessary to quantify the differences between different types of feet, are absent in literature, these properties were measured by the authors in a laboratory setup for nine different prosthetic feet, bare and with two different shoes. One test cycle consisted of measurements of load deformation curves in 66 positions, representing the range from heel strike to toe-off. The hysteresis is defined by the energy loss as a part of the total deformation energy. Without shoes significant differences in hysteresis between the feet exist, while with sport shoes the differences in hysteresis between the feet vanish for the most part. Applying a leather shoe leads to an increase of hysteresis loss for all tested feet. The stiffness turned out to be non-constant, so mean stiffness is used.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of desferrioxamine on reperfusion damage of rat heart mitochondria.

Ischaemia of the myocardium leads to necrosis unless oxygen supply is restored but it has only recently been realised that reperfusion is not without danger. The greatest rate of myocardial damage, as measured by mitochondrial function, occurred during the first 5 minutes of reperfusion in rat hearts subjected to normothermic ischaemic cardiac arrest. Addition of desferrioxamine to the perfusate after 5 minutes of reperfusion did not reverse the mitochondrial damage. It is therefore concluded that desferrioxamine prevents mitochondrial damage caused by ischaemia-reperfusion but does not reverse the damage already present.