Elimination of S100B and renal function after cardiac surgery.

OBJECTIVES: To determine the biologic half-life of the S100B protein and to investigate if the elimination of S100B depends on glomerular filtration rate (GFR). DESIGN: Prospective human study. SETTING: University hospital. PARTICIPANTS: Sixteen patients who underwent cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Shed mediastinal blood (autotransfusion) was returned to the patients postoperatively and used to study the kinetics of S100B. Iohexol was infused simultaneously to estimate GFR. S100B was measured at 0, 20, 40, 60, and 180 minutes after infusion. Iohexol was measured at 180 and 240 minutes after infusion. MEASUREMENTS AND MAIN RESULTS: S100B followed first-order kinetics, and the biologic half-life for S100B was determined to be 25.3 +/- 5.1 minutes. GFR was determined to be 63.8 +/- 34.4 mL/min. No correlation was found between GFR and S100B half-life. CONCLUSIONS: The elimination of S100B after cardiac surgery is faster than reported earlier and not affected by a moderate decrease in GFR. This finding is important when evaluating S100B levels after cardiac surgery.

S100beta after coronary artery surgery: release pattern, source of contamination, and relation to neuropsychological outcome.

BACKGROUND: S100beta has been suggested as a marker of brain damage after cardiac operation. The aim of this study was to characterize the early S100beta release in detail and relate it to neuropsychological outcome. METHODS: Three groups of patients were investigated. All patients underwent coronary artery bypass surgery (CABG) with extracorporeal circulation. In group A, 110 patients had sampling of S100beta for the first 10 postoperative hours and also underwent neuropsychological testing. In group B, 14 patients were examined for the effect of autotransfusion on S100beta levels. Eight patients in group C had their intraoperative bleeding processed with a cell-saving device. RESULTS: Group A had a heterogeneous release pattern with several rapid elevations in S100beta concentration. In group B, high concentrations of S100beta were found in the autotransfusion blood (range 0.2 to 210 microg/L) with a concurrent elevation of serum S100beta levels after transfusion of shed blood. In group C, high levels of S100beta were found in the blood from the surgical field (12.0+/-6.0 microg/L) and decreased (1.1+/-0.64 microg/L) after wash. Group C had significantly lower S100beta values at the end of cardiopulmonary bypass compared to group A (0.53+/-0.35 microg/L versus 2.40+/-1.5 microg/L). S100beta values were corrected for extracerebral contamination with a kinetic model. With this correction, an association was found between adverse neuropsychological outcome and S100beta release in group A (r = 0.39, p < 0.02). CONCLUSIONS: A significant amount of S100beta is found both in the blood from the surgical field and in the shed mediastinal blood postoperatively. Infusion of this blood will result in infusion of S100beta into the blood and interfere in the interpretation of early systemic S100beta values.

Protein kinase C-mediated phospholipase D activity is increased by linolenic acid supplementation in NG 108-15 cells.

Phospholipase D activation was studied in NG 108-15 cells after manipulation of the phospholipid fatty acid composition. Cultivation of cells in media containing different polyunsaturated fatty acids induced extensive and specific changes in the phospholipid fatty acid composition. General for all phospholipids was an increase in polyunsaturated fatty acids at the expense of monounsaturated fatty acids. To examine phospholipase D activation, cells were stimulated with phorbol esters in the presence of ethanol and the formation of phosphatidylethanol was analyzed. In cells cultured with linolenic acid, a significantly higher amount of phosphatidylethanol was formed compared to control cells. On the other hand, supplementation with linoleic, arachidonic or docosahexaenoic acids did not induce any changes in phospholipase D activity. The effect was not due to free fatty acids in the cell culture medium and thus probably induced by fatty acids incorporated into membrane phospholipids or fatty acid metabolites. The results indicate a specific effect of linolenic acid and/or its metabolites on protein kinase C-mediated phospholipase D activity.

Somatostatin28(15-28), but not somatostatin28(1-12), affects central monoaminergic neurotransmission in rats.

The effects of intracerebroventricularly (icv) administered somatostatin28(SS28) fragments, SS28(1-12) and SS28(15-28), were investigated on central monoaminergic neurotransmission in rats. SS28(15-28) did not significantly influence the hypothalamic and striatal noradrenaline concentrations. In a dose-related manner, SS28(15-28) significantly increased the dopamine, dihydroxyphenyl acetic acid DOPAC), and serotonin concentrations in hypothalamus, but did not modify these measures in striatum. The other SS28 metabolite, SS28(1-12), had no statistically significant effects on the monoamine neurotransmission. SS28(15-28) (6 and 9 nmol) induced barrel rotation, while SS28(1-12) was ineffective following administration over a wide dose-range (3-18 nmol). In conclusion, SS28(15-28) influences the hypothalamic monoaminergic transmission and causes barrel rotation, whereas SS28(1-12) has no neurochemical or behavioural effects in these tests.

Comparative studies of intracerebroventricularly administered cysteamine and pantethine in different behavioral tests and on brain catecholamines in rats.

In a passive avoidance test, intracerebroventricular administration (post-trial treatment) of the somatostatin-depleting compound cysteamine decreased the avoidance latency of the rats in a dose-related manner, while the effect of pantethine (which is metabolized to cysteamine) was less pronounced. In open-field studies, both compounds decreased the motor activity (ambulation, rearing) of the animals 15 min after the injection followed by a subsequent recuperation of the locomotor depression. Following pantethine, the ambulation increased during the later tests (60 min, 240 min, 24 hr). Cysteamine decreased the noradrenaline and increased the dopamine and dihydroxyphenyl acetic acid content in the hypothalamus, whereas the effects of pantethine were less expressed. Both compounds slightly decreased the striatal noradrenaline and increased the dihydroxyphenyl acetic acid levels at 15 and 60 min after administration. However, contrary to pantethine, 4 hr after treatment with cysteamine, there was a decrease in dihydroxyphenyl acetic acid concentration in this brain region. These findings suggest that both pantethine and cysteamine attenuate passive avoidance latency after intracerebroventricular treatment. The different efficiency of pantethine and its metabolite cysteamine might be connected to the low pantetheinase activity of the brain tissue; however, some direct effects of pantethine cannot be excluded. The different effects of the two compounds on the open-field activity are possibly associated with the diverse effects of the compounds on the striatal dopaminergic neurotransmission.

Dose- and time-response effects of pantethine on open-field behavior, and on central neurotransmission in rats.

In this study the dose- and time-related effects of pantethine on open-field behavior and central neurotransmissions were investigated in rats. Pantethine administered in low doses (0.48-0.96 mM/kg SC) only marginally influenced the activity of the animals, but induced a significant decrease of hypothalamic noradrenaline level without influencing the concentrations of dopamine and DOPAC. Injected in higher doses (1.95-3.90 mM/kg SC), the compound produced a marked depression of both open-field activity and noradrenaline levels, but increased the concentrations of dopamine and DOPAC in the hypothalamus. Twelve hr after the administration of the substance, its effect was attenuated, and 24 hr after the treatment neither the behavioral nor the monoamine parameters differed significantly from the control values. Concerning the somatostatin, pantethine administered in high doses (1.95-3.90 mM/kg SC) decreased the striatal concentration of somatostatin 4 hr after the injection, and this effect was attenuated 24 hr after the treatment. These data suggest that the pantethine-induced behavioral changes are correlated with its effect on central catecholaminergic and somatostatinergic transmission.

Effects of pantethine, cysteamine and pantothenic acid on open-field behavior and brain catecholamines in rats.

Cysteamine (1.95 mM/kg) markedly decreased the locomotor, rearing and grooming activities, as well as the number of defecation boluses in an open-field test. An equimolar dose of pantethine reduced the locomotor activity to a lesser extent, but has the same potency in decreasing the number of defecation boluses, whereas pantothenic acid did not affect the behavior of the rats. Cysteamine, and to a lesser extent pantethine, reduced the noradrenaline and increased the dopamine and DOPAC concentrations in the hypothalamus. Pantothenic acid itself did not influence the hypothalamic catecholamine concentrations. These results suggest that the lower efficacy of pantethine compared to cysteamine on both behavioral and neurochemical parameters is probably due to a rate-limiting activity of the enzyme pantetheinase in the conversion of pantetheine to cysteamine.

Effects of cysteamine and pantethine on open-field behavior, hypothalamic catecholamine concentrations, and somatostatin-induced barrel rotation in rats.

Cysteamine administered in a dose of 1.95 mM/kg subcutaneously (SC) markedly reduced several open-field behaviors (locomotion, rearing, grooming and defecation), while pantethine, administered in an equimolar dose, reduced the locomotion only. However, administered in a dose of 3.90 mM/kg (SC), pantethine also markedly reduced all open-field parameters. Cysteamine, and to less extent pantethine, reduced noradrenaline, and increased dopamine and DOPAC concentrations in the hypothalamus. It is discussed whether the lower potency of pantethine on open-field behaviors and hypothalamic catecholaminergic neurotransmission is connected with the limited activity of pantetheinase, the cysteamine-generating enzyme. Intracerebroventricularly (ICV) administered somatostatin did not influence the pantethine-induced (1.95 mM/kg SC) behavioral changes in the open-field test. It is possible that the peptide did not reach at the receptor sites in a sufficient concentration because of the reduced endogenous somatostatin content, or that the pantethine-induced noradrenaline depletion is connected with the ineffectiveness of somatostatin. Furthermore, pretreatment with cysteamine (1.95 mM/kg SC) or pantethine (1.95 mM/kg or 3.90 mM/kg SC) attenuated the somatostatin-induced (10 micrograms ICV) barrel rotation, suggesting that the level of endogenous somatostatin may play a role in the pathogenesis of this motor disturbance.