Discovery of an MIT-like atracotoxin family: Spider venom peptides that share sequence homology but not pharmacological properties with AVIT family proteins

This project identified a novel family of six 66-68 residue peptides from the venom of two Australian funnel-web spiders, Hadronyche sp. 20 and H. infensa: Orchid Beach (Hexathelidae: Atracinae), that appear to undergo N- and/or C-terminal post-translational modifications and conform to an ancestral protein fold. These peptides all show significant amino acid sequence homology to atracotoxin-Hvf17 (ACTX-Hvf17), a non-toxic peptide isolated from the venom of H. versuta, and a variety of AVIT family proteins including mamba intestinal toxin 1 (MIT1) and its mammalian and piscine orthologs prokineticin 1 (PK1) and prokineticin 2 PK2). These AVIT family proteins target prokineticin receptors involved in the sensitization of nociceptors and gastrointestinal smooth muscle activation. Given their sequence homology to MITI, we have named these spider venom peptides the MIT-like atracotoxin (ACTX) family. Using isolated rat stomach fundus or guinea-pia ileum organ bath preparations we have shown that the prototypical ACTX-Hvf17, at concentrations up to 1 mu M, did not stimulate smooth muscle contractility, nor did it inhibit contractions induced by human PK1 (hPK1). The peptide also lacked activity on other isolated smooth muscle preparations including rat aorta. Furthermore, a FLIPR Ca2+ flux assay using HEK293 cells expressing prokineticin receptors showed that ACTX-Hvf17 fails to activate or block hPK1 or hPK2 receptors. Therefore, while the MIT-like ACTX family appears to adopt the ancestral disulfide-directed beta-hairpin protein fold of MIT1, a motif believed to be shared by other AVIT family peptides, variations in the amino acid sequence and surface charge result in a loss of activity on prokineticin receptors. (c) 2005 Elsevier Inc. All rights reserved.

Prevalence and patterns of anxiety and depression in patients undergoing elective percutaneous transluminal coronary angioplasty

Background The use of elective percutaneous transluminal coronary angioplasty (PTCA) as a treatment for coronary heart disease is increasing. Despite this, little is known about the prevalence and patterns of anxiety and depression experienced by patients undergoing and recovering from this procedure. Anxiety and depression are factors known to negatively influence recovery after a cardiac event. Objective The purpose of this study was to (1) describe the levels of anxiety and depression reported by patients pre- and postelective PTCA, and (2) determine associations evident between anxiety and depression and the sociodemographic and clinical variables of gender, marital status, history of acute myocardial infarction, and attendance at cardiac rehabilitation. Methods In this descriptive, repeated-measures investigation, patients (n = 140) were requested to complete the Spielberger State Trait Anxiety Inventory and Cardiac Depression Scale (CDS) at three time points: 0(1) before admission for elective PTCA (T1); (2) 6 to 8 weeks (T2) after PTCA; and (3) 6 to 8 months (T3) after PTCA. Results A typical participant was male (75%), of European ethnicity (90%), aged 62 years (standard deviation = 10.7) with single or double vessel disease, and had attended cardiac rehabilitation in the past. At T1, 16% of men and 24% of women had state anxiety scores comparable to those experienced by neuropsychiatric patients. Trait anxiety scores remained relatively constant over time; higher scores at T1 were associated with past acute myocardial infarction. CDS scores at T2 and T3 were significantly lower than those at T1. However, an unexpected increase in CDS scores occurred at T3, compared with T2. At T3, 14% of men and 10% of women were depressed, relative to T1. Conclusion The findings lend support for the closer surveillance of emotional status in this population. Specialist nurses have the potential to play a greater role in identifying those at risk of developing anxiety and depression. However, this unmet need will remain unmet until specialist nurses who spend the most face-to-face time with patients are equipped with the skills and resources to systematically identify those “at risk.”