Effects of nifedipine on hepatic blood volume in cats: indirect venoconstriction and absence of inhibition of postsynaptic alpha 2-adrenoceptor responses

Intravenous administration of hypotensive doses (30-200 micrograms/kg) of nifedipine to cats anesthetized with pentobarbital caused an increase in cardiac output accompanied by hepatic venoconstriction. The hepatic venoconstriction and the increase in cardiac output were abolished in animals in which the hepatic sympathetic nerves were cut, the adrenal glands were excluded, and the kidneys were removed. This contrasts with the indirect hepatic venoconstrictor action of isoproterenol which was shown previously not to be abolished by these procedures. Further experiments showed that the hepatic venoconstrictor effect of nifedipine was blocked by removal of the kidneys, but not by removal of the hepatic sympathetic nerves and adrenals. These results support the hypothesis that venoconstriction plays an important role when drugs produce increased cardiac output. In nephrectomized animals, nifedipine had no direct effects on hepatic blood volume and it did not alter the effects of infusions of norepinephrine on hepatic blood volume, which have previously been shown to be mediated through alpha 2-adrenoceptors. However, it did reduce the hepatic venous responses to hepatic sympathetic nerve stimulation by 30%.     

Histochemical classification based upon reaction types and its application to carbohydrate histochemistry

Summary A method of classification is presented, which divides histochemical visualization reactions into categories based on general reaction types. This scheme is dependent upon the reaction between two elements, the substrate and the probe. The substrate represents a tissue component(s) with one or more reactive groups that can combine directly with the probe. Alternatively, the substrate reactive groups are chemically modified (activation) with a suitable reagent before reaction with the probe. Probes are of three types: those that yield a coloured product, those that result in a colourless product, and those that produce a coloured product only after a further reaction.Methods used in carbohydrate histochemistry are divided into one, two and three probe reactions. Two probe reactions are further subdivided into sequences involving one or two coloured products (one and two dye sequences); three probe reactions into sequences involving one, two or three coloured products (one, two and three dye sequences). This classification permits the rationalization and organization of methods, and provides a framework for the examination of existing methods and the development of new ones.     

Multiple Phenotypic Changes Associated with Large-Scale Horizontal Gene Transfer

Horizontal gene transfer often leads to phenotypic changes within recipient organisms independent of any immediate evolutionary benefits. While secondary phenotypic effects of horizontal transfer (i.e., changes in growth rates) have been demonstrated and studied across a variety of systems using relatively small plasmids and phage, little is known about the magnitude or number of such costs after the transfer of larger regions. Here we describe numerous phenotypic changes that occur after a large-scale horizontal transfer event (∼1 Mb megaplasmid) within Pseudomonas stutzeri including sensitization to various stresses as well as changes in bacterial behavior. These results highlight the power of horizontal transfer to shift pleiotropic relationships and cellular networks within bacterial genomes. They also provide an important context for how secondary effects of transfer can bias evolutionary trajectories and interactions between species. Lastly, these results and system provide a foundation to investigate evolutionary consequences in real time as newly acquired regions are ameliorated and integrated into new genomic contexts.     

Synthesis of Benzodioxinopyrroles as selective α2-adrenoceptor antagonists

A novel series of tetrahydrobenzodioxinopyrroles has been identified as potent and selective α₂-adrenoceptor antagonists. Convergent syntheses have been developed that allowed the preparation of analogues and their enantiomers. A compound of particular interest is the 5-fluoro substituted analogue (fluparoxan).