BACKGROUND AND OBJECTIVE A novel hypotensive peptide, adrenomedullin (AM), had recently been isolated, purifed and its encoding gene sequenced from a human phaeochromocytoma. In humans AM circulates in physiological levels and possesses a distinct vasodilatatory activity. The purpose of this study was to examine the behaviour of AM levels in primary adrenal failure. DESIGN Plasma AM levels were measured in patients with proven Addison's disease using a specific radioimmunoassay and compared to those in healthy normotensive subjects. PATIENTS Eighteen patients with Addison's disease (10 men and eight women; ages 21 to 72 years) and 21 healthy control subjects (13 men and eight women; ages 20 to 71 years) were enrolled in the study. All patients were studied under basal conditions and 10 were reassessed following corticosteroid treatment. RESULTS All patients with Addison's disease showed increased levels of AM compared to the control group. Mean plasma AM levels were correspondingly higher in patients with Addison's disease than in normal subjects (102.1±33.4 (SD) ng/l versus 13.7±6.1 ng/l; P<0.0001). In 10 patients studied after corticosteroid treatment, plasma AM levels were significantly reduced (P<0.0001: 110.3± 35.8 ng/l versus 32.4±10.3 ng/l) after 2 weeks of treatment. A weak correlation (r=0.458; P=0.048) was observed between systolic blood pressure and plasma AM concentrations in all patients with Addison's disease. CONCLUSIONS These results indicate a consistent but reversible increase of adrenomedullin in patients with Addison's disease.

Question: Vegetation around the alpine-treeline ecotone faces changes in both climate and land use (i.e. grazing abandonment). Broad-scale shrub encroachment is considered an effect of these changes, but it remains unclear how this process is mediated by local-scale environmental heterogeneity. Our goal is to determine which local-scale environmental factors shape the spatial distribution and temporal trends of alpine dwarf shrub vegetation dominated by Juniperus communis in Mediterranean mountains. Location: Three sites in the Central Apennine Mountain Range (Italy): Mt. Terminillo, Mt. Duchessa and Mt. Ernici. Methods: Combining a set of environmental variables obtained at a fine scale (25-m resolution) from multi-year remote sensing imagery and field-collected vegetation data, we modelled the occurrence and cover of Juniperus communis-dominated dwarf shrubland, as well as its change over time, as a function of local climate, topography and land use, using linear and generalized mixed effects models. Results: Over a period of almost 60 years (1954-2012) shrubland occurrence increased by 12% and shrubland cover by 10% in our study sites. Its current distribution and change over time appear to be strongly shaped by the joint influences of fine-scale topography, above-ground biomass, land use and microclimate. Shrublands have been favoured locally in areas with harsher alpine environmental constraints and stronger resource limitations. Conclusions:Our study shows that in the Mediterranean high-mountain environment J. communis dwarf shrubland acts as a stress-tolerant pioneer vegetation, occurring in areas that are otherwise sparsely vegetated. Contrary to our expectations, at fine scales, warmer temperatures and the regional decline in grazing did not favour shrub encroachment. Despite increasing overall, J. communis shrubs have little competitive ability to successfully encroach grasslands, and remain restricted to less-productive areas. Our results confirm that fine-scale environmental heterogeneity can strongly influence shrub distribution and dynamics, thereby modulating future responses in evolving alpine ecosystems.

Question: Vegetation in the alpine and treeline ecotone faces changes in both climate and land use. Shrub encroachment is considered an effect of these changes, but it′s still unclear how this effect is mediated by environmental heterogeneity. Our goal is to determine which environmental factors shape the fine-scale spatial distribution and temporal trends of alpine dwarf shrub. Location: Three sites in the Central Apennine, Italy. Methods: We used a comprehensive set of environmental factors across a broad temporal span to model, at a fine-scale, both (1) the current spatial distribution and (2) the change in shrub cover over the past 60 years. Results: Our results show that dwarf shrubs have generally increased in our study sites over the past 60 years, yet their distribution is strongly shaped by the joint influence of the fine-scale topography, productivity, land use and micro-climate. In particular, shrubs have been locally favored in areas with harsher alpine environmental constraints and stronger resource limitation. Instead, contrary to expectations, at this fine scale, warmer temperatures and the decline in grazing have not favored shrub encroachment. Conclusion: Dwarf shrubs appear as a stress-tolerant, pioneer vegetation that is currently distributed mainly over areas that are otherwise sparsely vegetated. It appears that shrubs exhibit poor competitive ability to invade grasslands and, though they have increased overall, they remain restricted to the least productive areas. Fine-scale environmental heterogeneity may strongly influence future responses of dwarf shrubs in changing alpine ecosystems.