Search for the glueball candidates f0(1500) and fJ(1710) in gamma gamma collisions

Data taken with the ALEPH detector at LEP1 have been used to search for gamma gamma production of the glueball candidates f0(1500) and fJ(1710) via their decay to pi+pi-. No signal is observed and upper limits to the product of gamma gamma width and pi+pi- branching ratio of the f0(1500) and the fJ(1710) have been measured to be Gamma_(gamma gamma -> f0(1500)). BR(f0(1500)->pi+pi-) < 0.31 keV and Gamma_(gamma gamma -> fJ(1710)). BR(fJ(1710)->pi+pi-) < 0.55 keV at 95% confidence level.Comment: 10 pages, 3 figure

Glucocorticoid receptor alters isovolumetric contraction and restrains cardiac fibrosis

Corticosteroids directly affect the heart and vasculature and are implicated in the pathogenesis of heart failure. Attention is focussed upon the role of the mineralocorticoid receptor (MR) in mediating pro-fibrotic and other adverse effects of corticosteroids upon the heart. In contrast, the role of the glucocorticoid receptor (GR) in the heart and vasculature is less well understood. We addressed this in mice with cardiomyocyte and vascular smooth muscle deletion of GR (SMGRKO mice). Survival of SMGRKO mice to weaning was reduced compared with that of littermate controls. Doppler measurements of blood flow across the mitral valve showed an elongated isovolumetric contraction time in surviving adult SMGRKO mice, indicating impairment of the initial left ventricular contractile phase. Although heart weight was elevated in both genders, only male SMGRKO mice showed evidence of pathological cardiomyocyte hypertrophy, associated with increased myosin heavy chain-β expression. Left ventricular fibrosis, evident in both genders, was associated with elevated levels of mRNA encoding MR as well as proteins involved in cardiac remodelling and fibrosis. However, MR antagonism with spironolactone from birth only modestly attenuated the increase in pro-fibrotic gene expression in SMGRKO mice, suggesting that elevated MR signalling is not the primary driver of cardiac fibrosis in SMGRKO mice, and cardiac fibrosis can be dissociated from MR activation. Thus, GR contributes to systolic function and restrains normal cardiac growth, the latter through gender-specific mechanisms. Our findings suggest the GR:MR balance is critical in corticosteroid signalling in specific cardiac cell types

New perspectives on evolutionary medicine: the relevance of microevolution for human health and disease

Evolutionary medicine (EM) is a growing field focusing on the evolutionary basis of human diseases and their changes through time. To date, the majority of EM studies have used pure theories of hominin macroevolution to explain the present-day state of human health. Here, we propose a different approach by addressing more empirical and health-oriented research concerning past, current and future microevolutionary changes of human structure, functions and pathologies. Studying generation-to-generation changes of human morphology that occurred in historical times, and still occur in present-day populations under the forces of evolution, helps to explain medical conditions and warns clinicians that their current practices may influence future humans. Also, analyzing historic tissue specimens such as mummies is crucial in order to address the molecular evolution of pathogens, of the human genome, and their coadaptations.Frank Jakobus Rühli and Maciej Henneber

Cinaciguat prevents the development of pathologic hypertrophy in a rat model of left ventricular pressure overload

Pathologic myocardial hypertrophy develops when the heart is chronically pressure-overloaded. Elevated intracellular cGMP-levels have been reported to prevent the development of pathologic myocardial hypertrophy, therefore we investigated the effects of chronic activation of the cGMP producing enzyme, soluble guanylate cyclase by Cinaciguat in a rat model of pressure overload-induced cardiac hypertrophy. Abdominal aortic banding (AAB) was used to evoke pressure overload-induced cardiac hypertrophy in male Wistar rats. Sham operated animals served as controls. Experimental and control groups were treated with 10 mg/kg/day Cinaciguat (Cin) or placebo (Co) p.o. for six weeks, respectively. Pathologic myocardial hypertrophy was present in the AABCo group following 6 weeks of pressure overload of the heart, evidenced by increased relative heart weight, average cardiomyocyte diameter, collagen content and apoptosis. Cinaciguat did not significantly alter blood pressure, but effectively attenuated all features of pathologic myocardial hypertrophy, and normalized functional changes, such as the increase in contractility following AAB. Our results demonstrate that chronic enhancement of cGMP signalling by pharmacological activation of sGC might be a novel therapeutic approach in the prevention of pathologic myocardial hypertrophy

A quantitative analysis of the effect of cycle length on arrhythmogenicity in hypokalaemic Langendorff-perfused murine hearts

The clinically established proarrhythmic effect of bradycardia and antiarrhythmic effect of lidocaine (10 μM) were reproduced in hypokalaemic (3.0 mM K+) Langendorff-perfused murine hearts paced over a range (80–180 ms) of baseline cycle lengths (BCLs). Action potential durations (at 90% repolarization, APD90s), transmural conduction times and ventricular effective refractory periods (VERPs) were then determined from monophasic action potential records obtained during a programmed electrical stimulation procedure in which extrasystolic stimuli were interposed following regular stimuli at successively decreasing coupling intervals. A novel graphical analysis of epicardial and endocardial, local and transmural relationships between APD90, corrected for transmural conduction time where appropriate, and VERP yielded predictions in precise agreement with the arrhythmogenic findings obtained over the entire range of BCLs studied. Thus, in normokalaemic (5.2 mM K+) hearts a statistical analysis confirmed that all four relationships were described by straight lines of gradients not significantly (P > 0.05) different from unity that passed through the origin and thus subtended constant critical angles, θ with the abscissa (45.8° ± 0.9°, 46.6° ± 0.5°, 47.6° ± 0.5° and 44.9° ± 0.8°, respectively). Hypokalaemia shifted all points to the left of these reference lines, significantly (P < 0.05) increasing θ at BCLs of 80–120 ms where arrhythmic activity was not observed (∼63°, ∼54°, ∼55° and ∼58°, respectively) and further significantly (P < 0.05) increasing θ at BCLs of 140–180 ms where arrhythmic activity was observed (∼68°, ∼60°, ∼61° and ∼65°, respectively). In contrast, the antiarrhythmic effect of lidocaine treatment was accompanied by a significant (P < 0.05) disruption of this linear relationship and decreases in θ in both normokalaemic (∼40°, ∼33°, ∼39° and ∼41°, respectively) and hypokalaemic (∼40°, ∼44°, ∼50° and ∼48°, respectively) hearts. This extended a previous approach that had correlated alterations in transmural repolarization gradients with arrhythmogenicity in murine models of the congenital long QT syndrome type 3 and hypokalaemia at a single BCL. Thus, the analysis in terms of APD90 and VERP provided a more sensitive indication of the effect of lidocaine than one only considering transmural repolarization gradients and may be particularly applicable in physiological and pharmacological situations in which these parameters diverge

Thrombospondins in the heart: potential functions in cardiac remodeling

Cardiac remodeling after myocardial injury involves inflammation, angiogenesis, left ventricular hypertrophy and matrix remodeling. Thrombospondins (TSPs) belong to the group of matricellular proteins, which are non-structural extracellular matrix proteins that modulate cell–matrix interactions and cell function in injured tissues or tumors. They interact with different matrix and membrane-bound proteins due to their diverse functional domains. That the expression of TSPs strongly increases during cardiac stress or injury indicates an important role for them during cardiac remodeling. Recently, the protective properties of TSP expression against heart failure have been acknowledged. The current review will focus on the biological role of TSPs in the ischemic and hypertensive heart, and will describe the functional consequences of TSP polymorphisms in cardiac disease

NADPH oxidases in cardiovascular disease: insights from in vivo models and clinical studies

NADPH oxidase family enzymes (or NOXs) are the major sources of reactive oxygen species (ROS) that are implicated in the pathophysiology of many cardiovascular diseases. These enzymes appear to be especially important in the modulation of redox-sensitive signalling pathways that underlie key cellular functions such as growth, differentiation, migration and proliferation. Seven distinct members of the family have been identified of which four (namely NOX1, 2, 4 and 5) may have cardiovascular functions. In this article, we review our current understanding of the roles of NOX enzymes in several common cardiovascular disease states, with a focus on data from genetic studies and clinical data where available

Measurement of the W mass in e+e−e^+ e^- collisions at 183 GeV

The mass of the W boson is obtained from reconstructed invariant mass distributions in W-pair events. The sample of W pairs is selected from 57 pb$^{-1}$ collected with the ALEPH detector in 1997 at a centre-of-mass energy of 183 GeV. The invariant mass distributions of reweighted Monte Carlo events are fitted separately to the experimental distributions in the $qqbarqqbar$ and all l\nuqqbar channels to give the following W masses: $m_{W}^{hadronic} = 80.461 \pm 0.177(stat.) \pm 0.045(syst.) \pm 0.056(theory) GeV/c^2$, $m_{W}^{semileptonic} = 80.326 \pm 0.184(stat.) \pm 0.040(syst.) GeV/c^2$ where the theory error represents the possible effects of final state interactions. The combination of these two measurements, including the LEP energy calibration uncertainty, gives $m_{W} = 80.393 \pm 0.128(stat.)\pm 0.041(syst.) \pm 0.028(theory)\pm 0.021(LEP) GeV/c^2