The influence of acetylsalicylic acid on cognitive processing: an event-related potentials study

The central effects of acetylsalicylic acid (ASA) are discussed controversially. In animal models, it has been shown that ASA can interact with the central serotonergic and catecholaminergic neuronal system. However, the relevance of this interaction for humans is still unknown. We performed a study on the influence of ASA on central cognitive processing. In 25 healthy subjects (age 21-56 years), visually evoked event-related potentials (ERP) and reaction time under IV ASA medication were recorded. ERP were evoked by an oddball paradigm. As compared to placebo, ASA decreased the latency of the P3 component significantly in a time interval of 20-40 min after administration. The latency of the N2 component was significantly decreased about 25 min after administration; the latency of the exogenous P2 component was not influenced by ASA. The mean choice reaction time was significantly decreased by ASA 35 min after administration. At this time point, there was a significant correlation between decrease in reaction time and increase in ASA plasma level. The data show that IV administration of ASA has an accelerating effect on the endogenous components of visual ERP and on reaction time. This finding suggests that ASA can influence central cognitive processing, possibly by ASA induced changes of neurotransmitters. Since serotonin can be released by ASA and serotonin release leads to a decrease of ERP latencies. we assume that ASA most likely influences cognitive processing via the central serotonergic transmitter system.     

Preparation and in vitro dissolution profile of dual polymer (Eudragit RS100 and RL100) microparticles of diltiazem hydrochloride

A microparticulate dosage form for a highly soluble drug, diltiazem hydrochloride, was formulated with Eudragit RS100 and RL100 using a novel dual polymer technique. A mixture of diltiazem with Eudragit RS100 (low water permeability) in acetone was coacervated into soft polymer microdrops, following which a mixture of diltiazem and RL100 (high water permeability) was added to produce microparticles consisting of both polymers with diltiazem dispersed in the matrix. A second formulation was developed using the same method except using Eudragit RS100 for both steps. For a comparative study, diltiazem, Eudragit RS100 and RL100 were combined together in a single matrix and formulated into microparticles. In vitro drug release profiles using USP paddle dissolution apparatus 2 revealed that dual polymer matrix microparticles containing Eudragit RS100 in the inner and Eudragit RL100 in the outer core exhibit a suitable release profile with an initial release of the drug followed by a plateau level for the test period of 5 h. Differential scanning calorimetric analysis showed no interaction of the drug with the polymers.     

Effects of ultrasound-assisted compaction on Ketoprofen/Eudragit S100 mixtures

Ketoprofen alone and in binary mixtures with Eudragit S100 was compacted by an ultrasound-assisted (US) tableting machine at an energy ranging from 50 to 400 J. The final material was analysed by TLC and HPLC: no decomposition product of the active agent was found. IR spectra and HSM revealed the absence of any interaction between the two components. Thermal analysis (DSC) evidenced that ketoprofen inside the mixtures was transformed into an amorphous state, documented by the decreasing of the DeltaHfus as the Eudragit/ketoprofen ratio increases and as US energy increases. While pure ketoprofen recovers its crystalline state quickly after the US treatment, the presence of Eudragit was found to slow down or possibly to prevent the regeneration of the crystallinity.     

The influence of mechanical stimuli and of acetylsalicylic acid on the discharges of slowly conducting afferent units from normal and inflamed muscle in the rat

In anaesthetized rats, the influence of an experimental inflammation and of acetylsalicylic acid (ASA) on the discharge properties of muscle receptors with slowly conducting afferent fibres was studied using a single-fibre recording technique. Following the induction of a myositis with carrageenan, the proportion of units having background activity and the frequency of the background discharge were significantly increased. The latter change was particularly prominent in high-threshold mechanosensitive (HTM) units. There was evidence for an inflammation-induced lowering of mechanical threshold in HTM units, but the change was not statistically significant. Administration of ASA intravenously led to a decrease in the frequency of background discharge in some units while others were unaffected, although they appeared to be sensitized by the inflammation. If one assumes that at least some of the HTM receptors fulfil nociceptive functions, the results suggest that the pain and tenderness of an inflamed muscle is largely due to a sensitization and hence increased activity of nociceptive muscle receptors. The sensitization is only partially abolished by ASA.     

The influence of the peptide chain on the kinetics and stability of microperoxidases

Microperoxidases with increasing lengths of the peptide attached to the heme moiety have been isolated after proteolytic digestion of horse-heart cytochrome c (microperoxidases 6, 8, and 11) and of cytochrome c550 from Thiobacillus versutus (microperoxidase 17). The different microperoxidases catalyze the H2O2-dependent para-hydroxylation of aniline relatively efficiently but are rapidly inactivated under turnover conditions. The horse-heart cytochrome-c-derived microperoxidases have identical values for Vmax but show a decrease of the K(m) for aniline and a higher stability when the attached peptide is longer. The kinetic constants obtained for microperoxidase 17, differ markedly from the microperoxidases derived from horse-heart cytochrome c. Possible factors underlying the observed differences are discussed.     

Effect of acetylsalicylic acid on metabolism and contractility in the ischemic reperfused heart

The effect of acetylsalicylic acid (ASA) on high-energy phosphates (adenosine triphosphate: ATP, creatine phosphate: CrP, inorganic phosphate: Pi) and intracellular pH during myocardial ischemia and reperfusion was studied using phosphorus 31-nuclear magnetic resonance (31P-NMR) in the isolated rabbit hearts. Coronary flow, left ventricular systolic developed pressure (LV Dev.P) and left ventricular end-diastolic pressure (LVEDP) were also measured. Langendorff hearts perfused at 37 degrees C with the perfluorochemical emulsion Fluosol-43 were subjected to 15 min and 30 min of zero-flow ischemia and to 15 min of low-flow ischemia (coronary perfusion pressure = 20 mmHg) followed by 65 min of reperfusion (control, Group I). ASA (0.28 mmol/L) was infused either for the entire experimental period from beginning 45 min prior to ischemia (Group II) and infused immediately after reperfusion (Group III). During ischemia, Group II showed a significant suppression of the decrease in the ATP level and pH with both zero-flow and low-flow ischemia compared to those in the other groups, and moreover the increase in Pi and the decrease in CrP in low-flow ischemia were also suppressed. In Group III, the ATP level during reperfusion was significantly higher than that in Group I, but was not significantly different from that in 30 min zero-flow ischemia. In 30 min zero-flow ischemia, Pi, CrP and coronary flow after reperfusion in Group II tended to recover to preischemic values. There were no differences in LV Dev.P among the 3 groups. In conclusion, ASA has a protective effect on myocardial high-energy phosphates during ischemia and reperfusion in rabbit hearts.     

The influence of tensile stress states on the failure of HY-100 steel

The failure of an HY-100 steel plate has been examined as a function of stress state using notched and un-notched axisymmetric tensile specimens. The results show that increasing stress triaxiality leads to a rapid decrease in failure strains in a manner that is exponentially dependent on the degree of triaxiality. Two ductile failure mechanisms are identified: a void coalescence process, in which relatively equiaxed voids grow to impingement, and a void-sheet process, which links by a shear instability process large, elongated inclusion-initiated voids. The void-sheet mechanism intervenes and limits ductility at high-stress triaxialities in transversely oriented HY steel plate material, whereas the former process controls failure in longitudinally oriented material. These orientation effects are related to the morphology and alignment of the nonmetallic inclusion stringers that act as the primary void nucleation sites. Calcium treatments for inclusion-shape control improve ductility, especially at intermediate-stress triaxialities, primarily by suppressing the local conditions which give rise to the void-sheet instability process.     

Effects of acetylsalicylic acid on plasma lipids and on post-heparin lipase activities

Acetylsalicylic acid (ASA) was administered orally at the dose of 3 g a day for 2 days to healthy subjects. Plasma free fatty acids, serum triglycerides and prebetalipoproteins were significantly decreased, while cholesterol, beta and alpha 1 lipoproteins did not change. The two fractions (protamine-resistant and protamine-inactivated) of plasma post-heparin lipoprotein lipase activity (PHLA) significantly fell after ASA. PHLA diminution was reproduced by direct addition of ASA or sodium salicylate or of plasma from individuals under treatment with ASA to post-heparin plasma of untreated subjects and is, therefore, explained by a direct inactivation. The inhibition of PHLA was not followed by a significant impairment of the removal of circulating triglycerides.     

Effect of acetylsalicylic acid on formalin test and on serotonin system in the rat brain

1. Acetylsalicylic acid (ASA; 400 mg/kg, i.p.) increased serotonin (5-HT) content in rat brain but did not modify the number or the affinity of 5-HT1A receptors in the pons and the cerebral cortex, whereas the number of cortical 5-HT2 receptors decreased significantly. 2. Pretreatment with parachlorophenylaline (100 mg/kg/day for 4 days) depleted 5-HT brain content but modified neither the serum levels of salicylates nor the 5-HT2 cortical receptor characteristics, and it abolished the antinociceptive effect of ASA, 400 mg/kg, in the first phase of the formalin test. 3. These data support the involvement of the central serotonergic system in the antinociceptive activity of ASA.     

Effects of mechanical activation on the kinetics of terbium leaching from waste phosphors using hydrochloric acid

The effect of mechanical activation(MA) on the kinetics of terbium(Tb) leaching from waste phosphors using hydrochloric acid was investigated. Leaching kinetics, such as apparent reaction rate, activation energy and reaction order, were determined using the shrinking-core model and the Arrhenius equation. Results obtained from experiments with different concentrations of HCl and under different leaching temperatures were used for the determinations. The impacts of factors such as rotational speed, HCl concentration and leaching temperature on the leaching rate of Tb were also discussed. The results showed that MA could dramatically increase the leaching rate of Tb from waste phosphors, and the apparent reaction rate(k_(ap)) of leaching was accelerated as well. For inactivated waste phosphors, the apparent activation energy(E_(ap)) was 52.82±3.95 kJ/mol, indicating that the rate-controlling step of the leaching process was the chemical reaction. The E_(ap) dropped to 25.96 ±3.90 kJ/mol and 10.96±2.79 kJ/mol when the waste phosphors were mechanically activated at rotational speeds of 400 and 600 r/min, respectively; the leaching process transformed to a hybrid(chemical-reaction and diffusion) control process, and even a reagent-diffusion(through the product layer) control process. The apparent reaction order for Tb leaching from 400 r/min-activated waste phosphors was 2.49±0.11, and it decreased to 1.16±0.17 when the rotational speed of 600 r/min was used. Kinetics results indicated that MA could make Tb leaching occur spontaneously, and the activation intensity of waste phosphors was strengthened with higher rotational speed.     

The influence of solutes on kinetics and thermodynamics of liquid indium-oxygen systems

The influence of small additions of the solutes Sn, Pb, Cu, Ag, and Ti on the diffusivity, solubility, activity, and the activity coefficient of oxygen in liquid indium was studied for temperatures between 750 and 950 °C, using solid state electrochemical techniques. A sharp increase in diffusivity and a decrease in solubility of oxygen were observed in all cases when small amounts of these solutes were added to liquid indium. Further additions of these solutes moderately increased the oxygen diffusivity and decreased the oxygen solubility. The thermodynamics of liquid binary alloys of indium, In-Sn, In-Pb, In-Cu, and In-Ag were also studied up to 10 at pct of these solutes. There is evidence that the large increase in diffusivity and decrease in solubility of oxygen in indium is due to cluster formations in liquid metal. Formerly with the Union Carbide Corporation,     

Nasal provocation tests in the diagnosis of urticaria induced by acetylsalicylic acid

Ciguatera fish poisoning is the most common form of toxin-related food poisoning in the United States. Originating from dinoflagellates living on coral reefs, it is spread up the food and affects humans who ingest the ciguatoxic fish. Ciguatera is primarily endemic in tropical regions of the world. It is a self-limiting disease that presents with characteristic gastrointestinal, neurological, and cardiovascular symptoms. Recent advances in testing procedures and symptom recognition has improved ciguatoxin identification and clinical management. However, there is still a need for better diagnostic, preventive, and reporting protocols to more accurately study and understand this diverse and temporarily debilitating clinical syndrome.     

Effect of acetylsalicylic acid on nitric oxide production in infarcted heart in situ

The effect of Acetylsalicylic Acid (ASA, Aspirin) on the myocardial production of the inducible form of nitric oxide synthase (iNOS) and the oxidation products of nitric oxide (nitrite, NO-2 and nitrate, NO-3: NOx) were studied in the rabbit heart two days after ligation of a branch of the left circumflex coronary artery. ASA was administered intravenously as AspisolR, DL-Lysinmono(acetylsalicylate) which is soluble in water. Animals received a total dose of 250, 375, or 500 mg/kg of ASA in five divided doses intravenously. Significant inhibition of iNOS was noted in the infarcted portion of the myocardium at 375 and 500 mg/kg of ASA. The reduction in myocardial nitric oxide (NO) production was paralleled by a diminution in coronary arterial-venous difference of NOx, demonstrating that ASA inhibition extended also to the oxidation products of NO. ASA is an inhibitor of cyclooxygenase (COX). The inhibition of iNOS by ASA demonstrates the close relationship between COX and iNOS activity in the heart in situ. Whether activity of the infarcted heart is influenced by the diminution in the production of NO by ASA is not known.     

The fetoplacental pressor effects of low-dose acetylsalicylic acid and angiotensin II in the ex vivo cotyledon model

OBJECTIVE: Our purpose was to investigate perfusion pressure changes ex vivo induced by angiotensin II on fetoplacental vasculature pretreated with low-dose acetylsalicylic acid. STUDY DESIGN: Two cotyledons from each of 12 placentas were perfused. The intervillous space of one cotyledon was infused with acetylsalicylic acid (5 x 10(-5) mol/L) similar to the serum concentration of women receiving daily low-dose aspirin therapy (60 to 81 mg). The control cotyledon was infused with an equivalent amount of normal saline solution. Two doses of angiotensin II, 1 x 10(-11.5) and 1 x 10(-10) moles, were injected as boluses into the chorionic arteries of each cotyledon. A 3 x 10(-7) mole dose of angiotensin II was also injected into the intervillous space. Statistical analysis was performed with analysis of variance, and results are expressed as mean pressure change in millimeters of mercury +/- SEM. RESULTS: Perfusion pressure response did not vary between cotyledons pretreated with acetylsalicylic acid and control cotyledons when 3 x 10(-7) moles of angiotensin II was injected into the intervillous space (8.0 +/- 1.9 mm Hg vs 9.8 +/- 1.6 mm Hg, p = 0.59). There were no differences between cotyledons in pressure response to 1 x 10(-11.5) moles of angiotensin II injected into the fetal circuit (5.9 +/- 0.8 mm Hg vs 6.7 +/- 0.9 mm Hg, p = 0.51). However, in the cotyledons pretreated with acetylsalicylic acid there was a decrease in the pressor response to 1 x 10(-10) moles of angiotensin II (14.1 +/- 1.4 mm Hg vs 21.5 +/- 3.3 mm Hg, p = 0.05). CONCLUSIONS: Low-dose aspirin infused into the intervillous space decreases vasoconstriction elicited by angiotensin II in the fetoplacental compartment. This suggests that maternal low-dose aspirin therapy has effects in the fetoplacental circulation in addition to its effects in the maternal circulation.     

Intrathecal injection of lysine acetylsalicylic acid in the rat: a neurotoxicological study

Lysine acetylsalicylic acid has been reported to induce analgesic effects in humans after intrathecal (i.t.) injection. Before conducting further studies in humans with this drug, it is important to evaluate potential toxicological effects on the spinal cord in animals. In the present study the effects of chronic intrathecal administration of provocative doses of lysine acetylsalicylic acid (L-ASA) on the rat spinal cord were evaluated using light and electron microscopy and a quantitative morphometric method. We also investigated the effects of single doses of the drug on the spinal cord blood flow (SCBF) using the laser-Doppler flowmetry technique. No histopathological changes or differences in number or density of neuronal cells could be seen after chronic administration of L-ASA as compared to controls. The SCBF decreased immediately after i.t. injection of a large dose (4 mg) of L-ASA and returned to predrug levels within 10 min. At the end of the experiment metabolic acidosis was detected, indicating a systemic effect of acetylsalicylic acid. It is concluded that no neurotoxic effects on the spinal cord were seen after chronic i.t. injection of L-ASA. From a neurotoxicological point of view, our findings do not contraindicate the spinal use of L-ASA in humans.