5-Hydroxytryptamine stimulates Rb efflux from pancreatic β-cells

The effects of 5-hydroxytryptamine and 5-hydroxytryptophan on ⁸⁶Rb⁺ efflux from prelabelled ob/ob-mouse islets were studied to better understand the cellular mechanisms underlying the effects of 5-hydroxytryptamine and 5-hydroxytryptophan on insulin release. 5-Hydroxytryptophan (4 mM) had no effect on ⁸⁶Rb⁺ efflux either at a low (3 mM) or at a high (20 mM) d-glucose concentration, whereas 5-hydroxytryptamine (4 mM) stimulated ⁸⁶Rb⁺ efflux at both glucose concentrations. These results indicate that 5-hydroxytryptamine may reduce glucose-induced insulin release by inhibiting early steps in the β-cell stimulus-secretion coupling.     

A new, transportable ergometer for the measurement of musculotendinous stiffness during wrist flexion.

We present here a new, dedicated mechanical device for monitoring quick-release movements of the wrist. The ergometer was designed to easily assess musculotendinous properties during wrist flexion. Maximal voluntary contractions (MVC) and quick-release (QR) movements during wrist flexion were performed on 14 subjects. A validation of the ergometer, using a test-retest methodology, was performed to assess its reliability and sensitivity. The device has been technically and biomechanically validated in a range of situations, including inertia measurement (mean inertia was found 0.0119+/-0.0012 N m s(2) rad(-1)) and appearance of the unloading reflex. Our results indicate that the device provides highly reliable, sensitive evaluation of wrist muscle stiffness (intraclass correlation coefficient for inertia, maximal voluntary contraction and stiffness index were 0.873, 0.994 and 0.930, respectively). Its portability facilitates measurement of the influence of repetitive, occupational activity on the musculotendinous complex of the wrist flexors.     

N alpha-arylsulfonyl-omega-amidinophenyl-alpha-aminoalkyl-carboxylic acid amides as specific thrombin inhibitors

Structure-activity relationships for the inhibition of thrombin and trypsin by N alpha-substituted amidinophenyl-alpha-aminoalkylcarboxylic acid amides are presented. Secondary cyclic amides of N alpha-substituted 4-amidinophenylalanine and 2-amino-5-(4-amidinophenyl)valeric acid were found to be potent and specific inhibitors of thrombin, whereas trypsin was inhibited strongly by primary amides of 2-amino-4-(4-amidinophenyl) butyric acid. For this type of inhibitor the carbon amide structure seems to play a decisive role in the enzyme-inhibitor interaction.     

Tyrant flycatchers coming out in the open: phylogeny and ecological radiation of Tyrannidae (Aves, Passeriformes)

Tyrant flycatchers constitute a substantial component of the land bird fauna in all South American habitats. Past interpretations of the morphological and ecological evolution in the group have been hampered by the lack of a well‐resolved hypothesis of their phylogenetic interrelationships. Here, we present a well‐resolved phylogeny based on DNA sequences from three nuclear introns for 128 taxa. Our results confirm much of the overall picture of Tyrannidae relationships, and also identify several novel relationships. The genera Onychorhynchus, Myiobius and Terenotriccus are placed outside Tyrannidae and may be more closely related to Tityridae. Tyrannidae consists of two main lineages. An expanded pipromorphine clade includes flatbills, tody‐tyrants and antpipits, and also Phylloscartes and Pogonotriccus. The spadebills, Neopipo and Tachuris are their closest relatives. The remainder of the tyrant flycatchers forms a well‐supported clade, subdivided in two large subclades, which differ consistently in foraging behaviour, the perch‐gleaning elaeniines and the sallying myiarchines, tyrannines and fluvicolines. A third clade is formed by the genera Myiotriccus, Pyrrhomyias, Hirundinea and three species currently placed in Myiophobus. Ancestral habitat reconstruction and divergence date estimation suggest that early divergence events in Tyrannida took place in a humid forest environment during the Oligocene. Large‐scale diversification in open habitats is confined to the clade consisting of the elaeniines, myiarchines, tyrannines and fluvicolines. This radiation correlates in time to the expansion of semi‐open and open habitats from the mid‐Miocene (c. 15 Mya) onwards. The pipromorphine, elaeniine and myiarchine–tyrannine–fluvicoline clades each employ distinct foraging strategies (upward striking, perch‐gleaning and sallying, respectively), but the degree of diversity in morphology and microhabitat exploitation is markedly different between these clades. While the pipromorphines and elaeniines each are remarkably homogenous in morphology and exploit a restricted range of microhabitats, the myiarchine–tyrannine–fluvicoline clade is more diverse in these respects. This greater ecological diversity, especially as manifested in their success in colonizing a wider spectrum of open habitats, appears to be connected to a greater adaptive flexibility of the search‐and‐sally foraging behaviour.     

Determination of the inorganic degradation products sulfate and sulfamate in the antiepileptic drug topiramate by capillary electrophoresis

A capillary electrophoresis (CE) method has been developed as an alternative method for the determination of the inorganic degradation products sulfate and sulfamate in topiramate drug product and drug substance, currently performed by ion chromatography. The anions are separated in a background electrolyte containing potassium chromate and boric acid, followed by indirect UV detection. By adding tetradecyltrimethylammonium bromide to the electrolyte, analysis is performed under co-electroosmotic flow conditions. Variations in injection volumes and migration times are compensated for by use of an internal standard. The validation of the method, which was performed according to ICH guidelines (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use) [1], comprises specificity, accuracy, linearity, precision, sensitivity and robustness. In addition, the results of an actual tablet sample analysis obtained by this CE method are statistically shown to be in close agreement with those obtained by an ion chromatographic method.