Synthesis and in vitro LTD4 antagonist activity of bicyclic and monocyclic cyclopentylurethane and cyclopentylacetamide N-arylsulfonyl amides

The dissociation constants (KB) at the LTD4 receptor on guinea pig trachea of a series of monocyclic and bicyclic cyclopentylurethane and cyclopentylacetamide N-arylsulfonyl amides have been measured. The KB was found to be remarkably tolerant of changes in the electronic constitution and lipophilicity of the bicyclic ring system (template). Thus, N-[4[[6-[[(cyclopentyloxy)carbonyl]amino]benzimidazol-1- yl]methyl]-3-methoxybenzoyl]benzenesulfonamide (11a) and N-[4-[[5-[[(cyclopentyloxy)carbonyl]amino]benzo[b]thien-3- yl]methyl]-3-methoxybenzoyl]benzene-sulfonamide (25a) had closely similar affinities (pKB, 9.20 and 9.31, respectively; LTE4 as agonist). It has been shown that the hetero-ring of the template need not be aromatic in order to achieve high affinity, since indoline 31 and 2,3-dihydrobenz-1,4-oxazines 37a-c had pKBs greater than 9. Further, it has been shown that an o-aminophenone (see 42 and Figure 3) can function as a template; the template in 42 [see iii] is bicyclic by virtue of the presence of an intramolecular hydrogen bond. In contrast, when the template is a phenyl ring (48), receptor affinity is markedly reduced. These findings support the notion that central bicyclic ring system in this family of peptidoleukotriene antagonists is a molecular feature which helps to preorganize the acylamino and acidic chains and thereby facilitate the molecular recognition event.     

L-694,247: a potent 5-HT1D receptor agonist.

1. The 5-hydroxytryptamine (5-HT) receptor binding selectivity profile of a novel, potent 5-HT1D receptor agonist, L-694,247 (2-[5-[3-(4-methylsulphonylamino)benzyl-1,2,4-oxadiazol-5-yl ]- 1H-indole-3-yl]ethylamine) was assessed and compared with that of the 5-HT1-like receptor agonist, sumatriptan. 2. L-694,247 had an affinity (pIC50) of 10.03 at the 5-HT1D binding site and 9.08 at the 5-HT1B binding site (sumatriptan: pIC50 values 8.22 and 5.94 respectively). L-694,247 retained good selectivity with respect to the 5-HT1A binding site (pIC50 = 8.64), the 5-HT1C binding site (6.42), the 5-HT2 binding site (6.50) and the 5-HT1E binding site (5.66). The pIC50 values for sumatriptan at these radioligand binding sites were 6.14, 5.0, < 5.0 and 5.64 respectively. Both L-694,247 and sumatriptan were essentially inactive at the 5-HT3 recognition site. 3. L-694,247, like sumatriptan, displayed a similar efficacy to 5-HT in inhibiting forskolin-stimulated adenylyl cyclase in guinea-pig substantia nigra although L-694,247 (pEC50 = 9.1) was more potent than sumatriptan (6.2) in this 5-HT1D receptor mediated functional response. L-694,247 (pEC50 = 9.4) was also more potent than sumatriptan (6.5) in a second 5-HT1D receptor mediated functional response, the inhibition of K(+)-evoked [3H]-5-HT release from guinea-pig frontal cortex slices.(ABSTRACT TRUNCATED AT 250 WORDS)     

Berechnung des Pflichtbeitrags eines niedergelassenen Arztes zum ?rztlichen Versorgungswerk bei Insolvenz

1. Wird dem Insolvenzsschuldner von den Gl?ubigern die Fortführung seiner Arztpraxis gestattet (sog. Betriebsfortführung), stellen die Pflichtbeitr?ge zur Altersversorgung sonstige Massenverbindlichkeiten dar, die gem. § 53 InsO vorweg durch den Insolvenzverwalter zu berichtigen sind. 2. Der Umstand, dass die Gl?ubigerversammlung im Rahmen der Betriebsfortführung für den fortführenden Arzt einen bestimmten monatlichen Unterhalt festgesetzt hat, bedingt keine Umqualifizierung der T?tigkeit als niedergelassener Arzt in eine Angestelltent?tigkeit. Die Pflichtbeitr?ge zur Altersversorgung sind daher nach den für Niedergelassene geltenden Satzungsbestimmungen zu berechnen, so dass nach wie vor allein der in der Praxis erzielte Gesamtumsatz und nicht der dem Arzt gew?hrte Unterhaltsbetrag als Berechnungsgrundlage für den Beitragssatz heranzuziehen ist.     

Spontaneous minute ventilation is a predictor of extubation failure in extremely-low-birth-weight infants.

OBJECTIVE: To validate the percentage of time spent below a target value of spontaneous expiratory minute ventilation (< 125 ml/min per kg) during a 2-h period of continuous positive airway pressure (CPAP) via an endotracheal tube (ETT) as a predictor of failed extubation in preterm infants. METHODS: Forty-one infants intubated for at least 24 h, with birth weight between 500 and 1000 g, who were clinically stable and at ventilator setting compatible with an extubation attempt, were studied during a 2-h period of ETT CPAP. Dynamic lung compliance and total lung resistance were measured during a period of quiet breathing, while tidal volume (Vt), respiratory rate and the corresponding spontaneous expiratory minute ventilation values were calculated for the complete recording period of 2 h using a customized computer program. The time each patient spent below the target spontaneous expiratory minute ventilation value was reported as a percentage of the total recorded time (% spontaneous expiratory minute ventilation < 125 ml/min per kg). Extubation failure was defined as the need for reintubation within 72 h. RESULTS: Eleven out of 41 babies (26.8%) experienced failure of extubation (failure group) while 30 infants (73.2%) were successfully extubated (success group). There were no significant differences in dynamic lung compliance and lung resistance between the two groups, but the mean values of respiratory rate and spontaneous expiratory minute ventilation were significantly lower in the failure group than in the success group: 43 (37-56) breaths/min and 240 (160-353) ml/min per kg vs. 53 (28-67) breaths/min and 309 (223-434) ml/min per kg, respectively (p = 0.0129 and p = 0.0039). Moreover, the babies in whom extubation failed spent a longer time below the target value of spontaneous expiratory minute ventilation when compared with successfully extubated babies (p < 0.0001). Percentage of time spent with spontaneous expiratory minute ventilation < 125 ml/min per kg had a larger area than transcutaneous (Tc)PCO2, TcPO2 and pulse oxymetry saturation (SpO2) under the receiver operator characteristic curves. CONCLUSION: The measurement of spontaneous expiratory minute ventilation prior to extubation could be useful in identifying those babies who are not ready for spontaneous ventilation.     

Vorrang des EU-Rechts im Approbationsrecht

1. Nach § 2 Abs. 1 S. 7 ZHG wird die Approbation nicht erteilt, wenn die naturwissenschaftliche Vorprüfung, die zahn?rztliche Vorprüfung oder die zahn?rztliche Prüfung nach der ZAppO endgültig nicht bestanden wurde. 2. Diese Regelung ist in Hinblick auf Art. 12 GG nicht zu beanstanden; allerdings bestehen gegen die Gültigkeit des § 2 Abs. 1 S. 7 ZHG verfassungsrechtliche Bedenken in Hinblick auf eine fehlende übergangs- bzw. Vertrauensschutzregelung.     

Keine Rundfunkgebühr für den Praxisweg

Abstrakt Fahrten eines Selbst?ndigen von seiner Wohnung zur Arbeitsstelle und zurück stellen eine „private“ Nutzung des Kraftfahrzeuges dar. In diesem Fahrzeug befindliche Zweitger?te unterfallen deshalb nicht gesondert der Rundfunkgebührenpflicht. (Leitsatz der Bearbeiterin)