Electrophysiologic effects of betaxolol on conduction properties of the antegrade and retrograde pathway in patients with typical atrioventricular node reentry tachycardia following intravenous and oral administration

The electrophysiologic effects of the beta-1 selective beta adrenergic blocking drug Betaxolol were investigated after intravenous (0.15 mg/kg body weight) and oral (20 mg/day) administration in 11 patients with atrioventricular-nodal reentrant tachycardia. Betaxolol significantly (p less than 0.01) prolonged cycle length, sinus node recovery time, AH-interval, as well as the antegrade functional refractory period of the slow and fast AV-nodal pathway. The effective refractory period of the fast AV-nodal pathway was also markedly increased (p less than 0.05). In only six patients could the effective refractory period of the slow AV-nodal pathway be determined; in the other patients, it was shorter than the effective refractory period of the atrium. The effective refractory period of the atrium and the ventricle was not significantly altered by Betaxolol. Intravenous administration of Betaxolol suppressed induction of tachycardia in eight patients, whereas after oral Betaxolol, tachycardia was not inducible in ten patients. Betaxolol prevented induction of tachycardia in two patients by prolonging antegrade conduction over the slow AV-nodal pathway. The retrograde fast AV-nodal pathway was blocked in eight patients. Presumably the increased effectiveness of oral Betaxolol can be attributed to higher Betaxolol plasma concentrations, reached after oral treatment (58 +/- 38 ng/ml), as compared to intravenous administration (40 +/- 40 ng/ml). There were no false positive results after intravenous testing of Betaxolol.     

Splicing of the mitochondrial group-II intron rl1: conserved intron-exon interactions diminish splicing efficiency

The mitochondrial intron rI1 is a self-splicing group-II intron of algal mitochondria that can be transferred into chloroplasts from the green alga Chlamydomonas reinhardtii for in vivo investigations (Herdenberger et al. 1994). Thus, rI1 is a suitable system to compare in vitro and in vivo RNA processing. Interestingly, rI1 shows correct RNA splicing, although typical cis-acting exon-sequences (IBS2, δ) of group-II introns are lacking. In order to examine the effect of these exon-intron interactions on splicing, we introduced the endogenous mitochondrial IBS2 sequence in order to produce optimal IBS2-EBS2 base pairing. In addition, the first nucleotide of the 3′exon (δ′) was substituted to create an optimal δ-δ′ interaction. Neither of the two mutations, nor a combination of both, had any effect on the precision of the splice-site selection. Unexpectedly, introduction of IBS2 led to a reduction in the efficiency of the second splicing step in vitro but not in vivo. These findings lead us to conclude that trans-acting factors are present in vivo to optimize splicing efficiency. The possibility is discussed that these factors may, for example, stabilize tertiary intron structures that are a prerequisite for correct RNA processing. Furthermore, our data indicate that similar trans-acting factors promote correct intron splicing in chloroplasts and mitochondria. Received: 18 October / 4 December 1997     

雌酮对蟾蜍神经—肌接头传递的影响

在蟾蜍离体坐骨神经－缝匠肌制备的肌细胞终板进行细胞内记录，研究了雌酮对神经－肌接头传递的影响。结果表明：雌酮加于浸浴液能增加１０μｇ筒箭毒处理组和１０ｍｍｏｌ／Ｌ ＭｇＣｌ２处理组制备的终板电位振幅，但前者的增加更显著；雌酮加入浸浴液３０分钟后引起小终板电位的振幅和频率明显增加，但波形不改变，静息膜电位也不改变。这些结果提示，雌酮能增加神经－肌接头传递，且主要通过突触前机理的作用。     

MAO-A inhibition in brain after dosing with esuprone, moclobemide and placebo in healthy volunteers: in vivo studies with positron emission tomography

Objective: The aim of the study was to investigate whether or not esuprone binds substantially to MAO-A in the human brain. Methods: In a randomised double-blind placebo-controlled study 16 male healthy volunteers were examined␣with positron emission tomography (PET) with [¹¹C]harmine. Eight of the volunteers were given daily doses of 800 mg esuprone, four were given bi-daily doses of 300 mg moclobemide, and four volunteers were given placebo tablets. PET was performed before initiation of a 7-day treatment period. On day 7, one investigation was made immediately before administration of the drug, representing 23 h after the previous day's treatment for esuprone and 11 h after the last tablets of moclobemide. Further investigations were made 4 h and 8 h after the morning dose on day 7. Results: PET showed a high degree of binding of [¹¹C]harmine, a high-affinity ligand for MAO-A, before the start of treatment, and a marked and similar reduction after treatment with esuprone and moclobemide. A slight tendency for normalisation of enzyme binding was observed at the last time point. In the placebo group no change was observed. Plasma kinetics of esuprone showed a rapid elimination with a half-life of about 4 h. Conclusion: The study demonstrates that esuprone was comparable to moclobemide in its effect on MAO-A inhibition in the brain at the doses given. This is an illustration of the potential of PET to monitor drug effects directly on target biochemical systems in the brain in human volunteers, and the possibility of using these data, rather than pharmacokinetic data, for the determination of dosing intervals. Received: 21 August 1996 / Accepted in revised form: 22 November 1996     

Temporal ranges of central nervous processing: clinical evidence

 The organization of the time frames for perceiving, generating, and updating information in the CNS has as of yet received little attention despite its elementary character for human behavior. We investigated temporal epochs in perceiving, acting, and updating in patients with anterior and posterior lesions of the left and right hemisphere, in patients with lesions in the left hemisphere without aphasia, and in healthy controls. Three temporal ranges, 30, 300, and 3000 ms, were assessed with different psychophysical paradigms. Prolongation of the temporal perception of order (30 ms) was most pronounced with left posterior lesions, of repetitive action (300 ms) with left anterior lesions, and updating (3000 ms) with left and right anterior lesions. Temporal deficits are group as well as parameter specific. Our results support the notion of coordinated coexistence of different temporal mechanisms.     

Reizhusten, Belastungsdyspnoe und zystische Lungenveränderungen bei einem 28jährigen Patienten

Zusammenfassung Eine neu aufgetretene Dyspnoesymptomatik und eine symmetrische, apikal betonte retikulonodul?re Zeichnungsvermehrung im R?ntgen-Thorax bei jungen rauchenden Erwachsenen müssen an das seltene Krankheitsbild der pulmonalen Histiocytosis X denken lassen. Klinischer Befund, laborchemische- und Lungenfunktionsuntersuchungen zeigen unspezifische Befunde. Neue radiologische Verfahren wie die hochaufl?sende Computertomographie (HRCT) leisten bei gezielter Indikationsstellung eine entscheidende differentialdiagnostische Hilfestellung. Dieser Fall verdeutlicht die M?glichkeit einer Diagnosesicherung durch transbronchiale Biopsien unter Verzicht auf offene Lungenbiopsien. Eine ambulante Diagnostik war m?glich, das h?here Risiko eines operativen Eingriffes konnte vermieden werden. Die Indikation zur Therapie ist nicht gesichert und wird daher durch den Grad der subjektiven bzw. funktionellen Einschr?nkung sowie den Verlauf bestimmt.     

Editorial

Ohne Zusammenfassung     

A path-analytical approach to differentiate between direct and indirect drug effects on negative symptoms in schizophrenic patients

The hypothesis that differences in drug effects of risperidone and haloperidol on negative symptoms in schizophrenia are secondary to effects on positive, extrapyramidal, and depressive symptoms was investigated by means of an analysis of the data from the USA-Canada risperidone double-blind randomized clinical trial of 523 chronic schizophrenic patients. Regression analyses in the total sample and within treatment groups confirmed a strong relationship between changes in negative symptoms and the other variables studied (R²=0.50–0.51,p<0.001). Only depressive symptoms did not contribute significantly to these results (p>0.10). Path analysis showed that the greater mean change (p<0.05) of negative symptoms with risperidone compared to haloperidol could not be fully explained by correlations with favourable effects on positive and extrapyramidal symptoms. The relationship between shift in extrapyramidal symptoms and shift in negative symptoms failed to reach statistical significance; however, there was a clear tendency in the expected direction in both treatment groups.     

CNS-active substances: synthesis of epoxybenzoxocines

The 2-(2-Bromophenyl)-acetaldehyde acetals 8 are treated with n-BuLi and the aldehydes 7 and 11 to form the hydroxyacetales 9 and 12, respectively. 9 is cyclized under acidic conditions to the epoxybenzoxocine 2; analogously 12 yields the epoxydibenzoxocine 14.