Intermedin (Adrenomedullin-2) a novel counter-regulatory peptide in the cardiovascular and renal systems

Intermedin (IMD) is a novel peptide related to calcitonin gene-related peptide (CGRP) and adrenomedullin (AM). Proteolytic processing of a larger precursor yields a series of biologically active C-terminal fragments, IMD1–53, IMD1–47 and IMD8–47. IMD shares a family of receptors with AM and CGRP composed of a calcitonin-receptor like receptor (CALCRL) associated with one of three receptor activity modifying proteins (RAMP). Compared to CGRP, IMD is less potent at CGRP1 receptors but more potent at AM1 receptors and AM2 receptors; compared to AM, IMD is more potent at CGRP1 receptors but less potent at AM1 and AM2 receptors. The cellular and tissue distribution of IMD overlaps in some aspects with that of CGRP and AM but is distinct from both. IMD is present in neonatal but absent or expressed sparsely, in adult heart and vasculature and present at low levels in plasma. The prominent localization of IMD in hypothalamus and pituitary and in kidney is consistent with a physiological role in the central and peripheral regulation of the circulation and water-electrolyte homeostasis. IMD is a potent systemic and pulmonary vasodilator, influences regional blood flow and augments cardiac contractility. IMD protects myocardium from the deleterious effects of oxidative stress associated with ischaemia-reperfusion injury and exerts an anti-growth effect directly on cardiomyocytes to oppose the influence of hypertrophic stimuli. The robust increase in expression of the peptide in hypertrophied and ischaemic myocardium indicates an important protective role for IMD as an endogenous counter-regulatory peptide in the heart.

Late referral for assessment of renal failure

It has been recommended that adult patients with a serum creatinine above 150 µmol/l should be referred to a nephrologist for specialist assessment. This study ascertained all patients in Northern Ireland with creatinine above this concentration in 2001 (n?=?19 286 ) to see if this triggered referral within the subsequent year. After exclusion of those who were already known to a nephrologist and those who had acute renal failure, it was found that younger patients and diabetic patients were more likely to be referred. There was no difference in referral rates between male and female patients. However, only 6.5% of all non-diabetic subjects and 19% of diabetic patients were referred within 12 months after a first increased serum creatinine test.

Association of Functional Heme Oxygenase-1 Gene Promoter Polymorphism with Renal Transplantation Outcomes

Heme oxygenase-1 (HO-1) is a cytoprotective molecule and increased expression in experimental transplant models correlates with reduced graft injury. A functional dinucleotide repeat (GT)n polymorphism, within the HO-1 promoter, regulates gene expression; a short number of repeats (S-allele