Impaired endothelial progenitor cell function predicts age-dependent carotid intimal thickening

Objectives  We investigated whether qualitative or quantitative alterations of the endothelial progenitor cell (EPC) pool predict age-related structural vessel wall changes. Background  We have previously shown that age-related endothelial dysfunction is accompanied by qualitative rather than quantitative changes of EPCs. Animal studies suggest that impaired EPC functions lead to accelerated arterial intimal thickening. Methods  Intima-media thickness (IMT) was measured in the common carotid artery in our previously published groups of younger (25 ± 1 years, n = 20) and older (61 ± 2 years, n = 20) healthy non-smoking volunteers without arterial hypertension, hypercholesterolemia, and diabetes mellitus. Endothelial progenitor cells (EPCs, KDR⁺/CD34⁺ and KDR⁺/CD133⁺) were counted in peripheral blood using flow cytometry. In ex vivo expanded EPCs, the function was determined as chemotaxis to VEGF, proliferation, and survival. Results  We observed thicker IMT in older as compared to younger subjects (0.68 ± 0.03 mm Vs. 0.48 ± 0.02 mm, P < 0.001). Importantly, there were significant inverse univariate correlations between IMT, EPC chemotaxis, and survival (r = −0.466 P < 0.05; r = −0.463, P < 0.01). No correlation was observed with numbers of circulating EPCs. Multivariate regression analysis revealed that age, mean arterial pressure and migration of EPCs were independent predictors of IMT (R ² = 0.58). Conclusion  Impaired EPC function may lead to accelerated vascular remodeling due to chronic impairment of endothelial maintenance. Returned for 1. Revision: 13 December 2007 1. Revision received: 16 June 2008 Returned for 2. Revision: 20 June 2008 2. Revision received: 17 July 2008     

The L-arginine-nitric oxide pathway in hypertension

Nitric oxide is involved in the regulation of resting vascular tone, adaptation of blood flow to metabolic demand of tissue, and adaptation of vessel diameter to volume of inflow, ie, flow-mediated dilation. Arterial hypertension is associated with an increased vascular tone of resistance vessels, a reduced compliance of conduit arteries, along with a thickening of the intima-media leading to vascular remodeling. Dysfunctional endothelium triggers such maladaptive processes. A reduced bioavailability of nitric oxide has been shown in hypertensive individuals dependent on the duration and severity of arterial hypertension. Angiotensin-converting enzyme inhibitors reverse endothelial dysfunction, whereas a concomitant reduction in significant cardiac events due to improved bioavailability has yet to be established. Long-term follow-up studies in individuals with manifest endothelial dysfunction and in offspring from hypertensive patients underscore the prognostic and genetic significance of a reduced nitric oxide bioavailability for the pathophysiology of arterial hypertension.     

Neuropeptide Y (NPY)

Neuropeptides such as neuropeptide Y (NPY) have long been proposed to play a role in the pathogenesis of inflammatory diseases. NPY is a 36 amino acid neuropeptide which participates in the regulation of a large number of physiological and pathophysiological processes in the cardiorespiratory system, immune system, nervous system and endocrine system. Serum levels of NPY are increased during exacerbations of asthma, whereas the number of NPY-immunoreactive nerves in the airways remains constant in the airways of patients with inflammatory airway diseases such asthma or rhinitis. Next to a role in the regulation of glandular activity, NPY exerts a major influence on humoral and cellular immune functions. In this respect, NPY is known to modulate potent immunological effects such as immune cell distribution, T helper cell differentiation, mediator release, or natural killer cell activation. In addition to these direct effects, NPY also acts as an immunomodulator by influencing the effects of a variety of other neurotransmitters. Whereas the peptide has been focused for therapeutic options in the central nervous system, a potential use in the treatment of pulmonary inflammatory disorders has not been revealed so far due to the complex pulmonary effects of NPY. However, since selective antagonists and agonists and gene-depleted animals for the different receptors are now available, NPY may be of value for future strategies in airway nerve modulation.     

Cryocatheter ablation of right ventricular outflow tract tachycardia

INTRODUCTION: Cryocatheter techniques have been successfully applied to treat supraventricular tachycardia but there are no reports on their value in treating ventricular tachycardia (VT). We present our initial experience with cryocatheter ablation of right ventricular outflow tract (RVOT) tachycardia. METHODS AND RESULTS: Cryocatheter ablation was attempted in 14 patients (13 females, age 45.9 +/- 12.7 years) who were highly symptomatic due to frequent monomorphic ventricular extrasystole (VES) or nonsustained VT originating within the RVOT. A 9-Fr, 8-mm-tip cryocatheter was used for both mapping and ablation. Cryoablation was started after localizing the arrhythmic focus by pace and activation mapping. Ablation success, defined by complete disappearance of target VES/VT acutely and during a follow-up of 9.3 +/- 1.4 weeks, was achieved in 13 of 14 patients. Ablation was successful with local activation times of 35 +/- 4 ms, 5.8 +/- 3.3 applications, 18.8 +/- 7.5 minutes total cryo time, 9.4 +/- 4.2 minutes fluoroscopy time, and 66.9 +/- 26.1 minutes total procedure time, the latter two measures showing a reduction with number of patients treated. Three patients reported slight pain related to local pressure of the catheter on the RVOT wall. No pain was described related to delivery of cryothermal energy. CONCLUSIONS: Initial experience shows that focal VES/VT originating in the RVOT can be successfully treated using cryocatheter ablation. Acute and short term success rates, fluoroscopy times, and duration of procedure are comparable to conventional ablation techniques. A major advantage seems to be the virtual absence of ablation related pain.     

Late sequelae of retained foreign bodies after world war II missile injuries

A number of people injured during the second world war harbour foreign bodies such as grenade splinters or bullets in some part of the body. Most of these metal fragments remain clinically silent. Some of them, however, may cause delayed complications. The purpose of this study was to determine the characteristics of delayed complications associated with foreign bodies after world war II injuries. 159 patients with retained foreign bodies after world war II injuries were retrospectively identified radiologically in our data bases in the time interval from 1997 to 2009. Diverse delayed complications secondary to the metal objects were diagnosed in 3 cases (2%): one patient with grenade splinter migration into the choledochal duct, one case with pseudotumoural tissue reaction, and one patient with late osteomyelitis. The time from injury to clinical presentation varied from 56 to 61 years. PubMed and Medline were screened for additional cases with delayed sequelae after foreign body acquisition during the 2nd world war. A 30 year search period from 1980 up to date was selected. 15 cases were identified here. Our study demonstrates that health consequences of the 2nd world war extend into the present time, and therefore physicians should be aware of the presence of hidden foreign bodies and their different possible late reactions.     

Longevity for free? Increased reproduction with limited trade-offs in Drosophila melanogaster selected for increased life span

Selection for increased life span in Drosophila melanogaster has been shown to correlate with decreased early fecundity and increased fecundity later in life. This phenomenon has been ascribed to the existence of trade-offs in which limited resources can be invested in either somatic maintenance or reproduction. In our longevity selection lines, we did not find such a trade-off. Rather, we find that females have similar or higher fecundity throughout life compared to non-selected controls. To determine whether increased longevity affects responses in other traits, we looked at several stress resistance traits (chill coma recovery, heat knockdown, desiccation and starvation), geotactic behaviour, egg-to-adult viability, body size, developmental time as well as metabolic rate. Longevity selected flies were more starvation resistant. However, in females longevity and fecundity were not negatively correlated with the other traits assayed. Males from longevity selected lines were slower at recovering from a chill induced coma and resting metabolic rate increased with age, but did not correlate with life span.