Anti-inflammatory effects of the activation of the angiotensin-(1-7) receptor, MAS, in experimental models of arthritis

Activation of the renin-angiotensin (Ang) system induces inflammation via interaction between Ang II and type 1 receptor on leukocytes. The relevance of the new arm of the renin-Ang system, namely Ang-converting enzyme-2/Ang-(1-7)/Mas receptor, for inflammatory responses is not known and was investigated in this study. For this purpose, two experimental models were used: Ag-induced arthritis (AIA) in mice and adjuvant-induced arthritis (AdIA) in rats. Male C57BL/6 wild-type or Mas(-/-) mice were subjected to AIA and treated with Ang-(1-7), the Mas agonist AVE 0991, or vehicle. AdIA was performed in female rats that were given AVE 0991 or vehicle. In wild-type mice, Mas protein is expressed in arthritic joints. Administration of AVE 0991 or Ang-(1-7) decreased AIA-induced neutrophil accumulation, hypernociception, and production of TNF-α, IL-1β, and CXCL1. Histopathological analysis showed significant reduction of inflammation. Mechanistically, AVE 0991 reduced leukocyte rolling and adhesion, even when given after Ag challenge. Mas(-/-) mice subjected to AIA developed slightly more pronounced inflammation, as observed by greater neutrophil accumulation and cytokine release. Administration of AVE 0991 was without effect in Mas(-/-) mice subjected to AIA. In rats, administration of AVE 0991 decreased edema, neutrophil accumulation, histopathological score, and production of IL-1β and CXCL1 induced by AdIA. Therefore, activation of Mas receptors decreases neutrophil influx and cytokine production and causes significant amelioration of arthritis in experimental models of arthritis in rats and mice. This approach might represent a novel therapeutic opportunity for arthritis.     

Unstimulated and Amphetamine-Stimulated Release of Endogenous Noradrenaline and Dopamine from Rat Brain In Vivo

Abstract: The in vivo release rates of endogenous noradrenaline from the hypothalamus and dopamine from the caudate nucleus of the rat have been determined. Artificial CSF perfusates collected from a push-pull cannula inserted into specific areas of the brain were assayed for the amines by a sensitive radioenzymatic procedure. The release rates of noradrenaline and dopamine into artificial CSF perfusates were 38 ± 6 and 46 ± 6 pg/h (225 ± 36 and 301 ± 39 fmol/h), respectively; when 0.5 mM amphetamine was added to the CSF, the release rates of noradrenaline and dopamine increased to 176 ± 50 and 1183 ± 453 pg/h (1041 ± 296 and 7732 ± 2961 fmol/h), respectively.     

Chromosome walking with YAC clones in Arabidopsis: isolation of 1700 kb of contiguous DNA on chromosome 5, including a 300 kb region containing the flowering-time gene CO

The co mutation of Arabidopsis thaliana causes a late-flowering phenotype that is insensitive to day-ength. The mutation was mapped previously to the upper arm of chromosome 5, approximately 1.6 cM from the chalcone synthase gene (CHS). We were provided with five yeast artificial chromosome (YAC) libraries and used these to perform a chromosome walk from CHS to the CO gene. In this paper we report the isolation of 1700 kb of contiguous Arabidopsis DNA, which represents approximately 1%–2% of the genome, inserted in YACs. This required the detailed analysis of 67 YACs, from which 87 end probes were isolated and examined in hybridisation experiments. This analysis showed that approximately 40% of the YACs presented problems in chromosome walking experiments because they contained repetitive sequence at one of their termini, were chimaeric or because part of the plant DNA was deleted. DNA fragments isolated from YACs were used as restriction fragment length polymorphism (RFLP) markers to localize CO to a 300 kb region within the cloned DNA. We compare the physical distance between CHS and CO with the genetic distance and find that in this region 1 cM is equivalent to approximately 200 kb.     

What is the significance of herbicide-nutrient interactions on wheat?

Sulfonylurea herbicides have been found to decrease the uptake and utilization of some nutrients by wheat. This paper reviews the effects of sulfonylureas on nutrient uptake, proposes physiological mechanisms which might explain the effects; and examines the agronomic implications.     

Calculation of the conformation of glycosphingolipids. 1. Beta-D-glucosyl-N-(2-D-hydroxyoctadecanoyl)-D-dihydrosphingosine (glucosyl-ceramide) and alpha-D-N-acetylneuraminyl-(2----3)-beta-D-galactose

The conformation of a glucosyl-ceramide, beta-D-galactosyl-N-(2-D-hydroxyoctadecanoyl)-D-dihydrosphingos in e, and of the disaccharide, N-acetylneuraminyl-galactose have been predicted by energy minimization techniques including an orbital force field approach. The predictions have been shown to be in excellent agreement with the results of X-ray single crystal analysis and structures postulated from nuclear magnetic resonance methods and have confirmed the utility of the computational approach to the study of glycosphingolipids.     

Short-term effects of manipulating the source:sink ratio of white clover (Trifolium repens) plants on export of carbon from, and morphology of, developing leaves

The source:sink ratio of clonal white clover ( Trifolium repens L.) plants was manipulated by shading or removing leaves, and the consequences for carbon export from, and for the weight, area and net photosynthesis of, developing leaves were determined. When treatments were imposed just before young leaves usually change from C sinks to C sources, no effect on the point at which the sink-to-source transition occurred was observed, Leaves exported a similar proportion of the C they fixed, irrespective of stresses imposed upon the rest of the plant. However, differences in the destination of exported C were observed. More C moved to the stolon apex, and less to the stolon tissue itself, from leaves at Carlson stage 0.8 (leaflets about 60% unfolded) when mature leaves were removed or shaded. When 2 out of 3 mature leaves were removed from a stolon, short-term responses such as a 10% increase in net photosynthesis of the residual mature leaf, and greater export of C from this leaf to the apex, partially compensated very young leaves for loss of C supply. The result was that, when these young leaves were fully unfolded, they had similar surface area to those which had developed on undefoliated plants, but weighed nearly 20% less. Thus the immediate response to defoliation was an increase in the speeific leaf area [cm² (g of dry weight)⁻¹] of new leaves, and the assimilation rate (net photosynthesis×area) of these leaves remained unchanged.