The N400 as a function of the level of processing

In a semantic priming paradigm, the effects of different levels of processing on the N400 were assessed by changing the task demands. In the lexical decision task, subjects had to discriminate between words and nonwords and in the physical task, subjects had to discriminate between uppercase and lowercase letters. The proportion of related versus unrelated word pairs differed between conditions. A lexicality test on reaction times demonstrated that the physical task was performed nonlexically. Moreover, a semantic priming reaction time effect was obtained only in the lexical decision task. The level of processing clearly affected the event-related potentials. An N400 priming effect was only observed in the lexical decision task. In contrast, in the physical task a P300 effect was observed for either related or unrelated targets, depending on their frequency of occurrence. Taken together, the results indicate that an N400 priming effect is only evoked when the task performance induces the semantic aspects of words to become part of an episodic trace of the stimulus event.     

Cyclic disulfide analogues of the complement component C3a Synthesis and conformational investigations

The flexible C-terminal region of the anaphylatoxic peptide C3a was reported to contain the receptor binding site. To elucidate the receptor binding conformation of the C-terminus, as well as to examine a synthetic approach to potential C3a-antagonists, 26 cyclic disulfide bridged C3a analogues were synthesized. Solid phase peptide synthesis was performed on different polymeric supports by individual peptide synthesis, with Fmoc strategy, and simultaneous multiple peptide synthesis, using Boc and Fmoc strategies. Both strategies gave open-chain peptides in comparable yields. Syntheses using the Boc strategy employed the HF-labile 4(methoxy)benzyl group (Mob) for β-thiol protection of cysteine; in contrast, the TFA-stable protecting groups, acetamidomethyl (Acm) and trityl (Trt), were chosen for syntheses employing Fmoc strategy. Ring closure reactions by iodine oxidation were carried out starting from protected (Acm/Acm, Trt/Acm) or unprotected dithiols. The resulting cyclic C3a analogues were characterized by HPLC, amino acid analysis, and FAB-MS. Conformational investigations using CD spectroscopy and theoretical structural investigations by means of molecular dynamics calculations revealed that slight variations in sequence result in pronounced conformational consequences. The potential of cyclic C3a analogues to activate or to desensitize guinea pig platelets, a standard test system for biological activities of anaphylatoxic peptides like C3a, revealed relatively low activities for cyclic peptides (<0.1% C3a activity). N-terminal acylation with cationic, arginine-rich sequences like YRRGR- led to amplified biological effects. Three of the synthesized peptides, namely CAALCLAR (P1), YRRGR°CGGLCLAR (P5) and YRRGRAhx°CGGLCLAR (P8), point in the direction of C3a antagonists.     

Comparison of Procedures for Measuring the Quaternary N-Glucuronides of Amitriptyline and Diphenhydramine in Human Urine with and without Hydrolysis

The activities of β-glucuronidases from Helix pomatia, Escherichia coli and rat towards the N-glucuronides of amitriptyline and diphenhydramine were considerably lower than those towards standard substrates. The two N-glucuronides were analysed in urine samples by the following procedures: HPLC of the intact conjugate after solid-phase extraction on a cation exchanger cartridge or after direct injection of urine; HPLC of the aglycone after hydrolysis with β-glucuronidase from H. pomatia or E. coli or after alkaline hydrolysis. Solid-phase extraction led to the highest recovery and precision, and sensitivity can be improved by extracting a larger volume of urine. On application to samples from patients under treatment with amitriptyline, the results of all procedures except alkaline hydrolysis were in good agreement. When diphenhydramine N-glucuronide was analysed in urine samples of volunteers, solid-phase extraction, hydrolysis by E. coli glucuronidase and alkaline hydrolysis resulted in similar values.     

Impact of Occluder Device Type on Success of Percutaneous Closure of Atrial Septal Defects–A Medium‐Term Follow‐up Study

Objective: To identify differences between various occluder types regarding thromboembolic event rates and existence of residual shunts during medium‐term follow‐up. Methods: Three hundred nine consecutive patients with presumed paradoxical embolism and scheduled for percutaneous closure of patent foramen ovale or atrial septal defect between 1997 and 2006 were considered for this study. Device implantation failed in seven patients (nonstable device position), so 302 patients (46 ± 12 years, 190 males) formed the study group using Amplatzer? (n = 208), Starflex? (n = 61), and Cardiastar? (n = 33) occluders. Follow‐up transesophageal echocardiography was performed 1, 3, and 6 months after implantation. Results: Periinterventional complications occurred in two patients (cardiac arrhythmias). There were more residual shunts in the Starflex? and Cardiastar? group than in the Amplatzer? group at 6‐month follow‐up (8/61 vs. 7/33 vs. 8/208, P = 0.0005). Performing logistic regression, the type of occluder device was a significant risk factor for the presence of residual shunt 6 months after implantation (P = 0.0033; Cardiastar? vs. Amplatzer? OR 6.346, 95% CI 1.998 – 20.156; Starflex? vs. Amplatzer? OR 4.369, 95% CI 1.444 – 13.222). During mean follow‐up of 31 ± 8 months 16 recurrent thromboembolic events occurred; the annual recurrence was 2.1% for combined end‐point stroke, TIA, and peripheral embolism (Amplatzer?: 1.3%, Starflex?: 3.9%, and Cardiastar?: 3.6%, P = 0.0467). The presence of an atrial septal aneurysm was the only significant risk factor (P = 0.0168, OR 3.664, 95% CI 1.263 – 10.630) for the occurrence of thromboembolic events. Conclusions: Percutaneous closure of patent foramen ovale or atrial septal defect is a safe procedure with little incidence of peri‐ and postprocedural complications. There is a significant difference between the Amplatzer?, Cardiastar?, and Starflex? occluders in regard to complete closure of the defects and annual recurrence of thromboembolic events.