Association of the ScaI atrial natriuretic peptide gene polymorphism with nonfatal myocardial infarction and extent of coronary artery disease

Background There is growing evidence from recent studies that atrial natriuretic peptide (ANP) plays an important part in coronary blood flow regulation and in atherosclerosis. Transition T2238→C in the atrial natriuretic peptide (ANP) precursor gene, which leads potentially to the translation of ANP with 2 additional arginines, has been suggested to be associated with salt-sensitive hypertension. According to our knowledge, this study is the first to look for the potential association of the ScaI ANP gene polymorphism with the history of nonfatal myocardial infarction and the extent of coronary artery disease (CAD).Methods The study was performed in 847 consecutive, white patients (719 men and 128 women) with significant coronary artery stenosis confirmed by means of elective coronary angiography (at least 1 coronary artery with ≥50% lumen narrowing). Screening for the T2238→C substitution was performed by means of polymerase chain reaction of genomic DNA, followed by ScaI digestion and agarose gel electrophoresis.Results We found a significant association of the A2A2 ScaI ANP genotype with a higher incidence of positive history of nonfatal myocardial infarction (odds ratio 1.85, 95% CI 1.33-2.58) and multiple-vessel CAD (odds ratio 1.45, 95% CI 1.02-2.06). The ScaI ANP genotype distribution did not differ with age, sex, body mass index, plasma lipids, hypertension, diabetes mellitus, and family history of CAD in studied groups.Conclusions Our results suggest that the ScaI ANP polymorphism may be associated with nonfatal myocardial infarction and the extent of CAD. However, the precise mechanism of this association remains to be determined. (Am Heart J 2003;145:125-31.)     

Percutaneous peripheral interventions in patients with non-ST elevation acute coronary syndromes performed by interventional cardiologists: rationale and results

BACKGROUND: The coexistence of peripheral artery disease (PAD) and multilevel atherosclerosis increases death and stroke rates in patients with coronary artery disease (CAD). Due to many comorbidities these patients are often treated conservatively without revascularisation. AIM: To investigate whether complex percutaneous cardiovascular interventions for CAD and PAD may improve prognosis and long-term outcome in this group of patients. METHODS: We studied consecutive patients treated for symptomatic CAD who also had chronic PAD. The primary cause of hospital admission for all our patients was non-ST elevation acute coronary syndrome (NSTE ACS). All percutaneous peripheral interventions were performed during one hospital stay (index hospitalisation). Major adverse cardio- and cerebrovascular events (MACCE) during follow-up were defined as follows: death (cardiac and non-cardiac), myocardial infarction (MI), urgent revascularisation (surgical or repeat PCI, peripheral percutaneous intervention), stroke/TIA or amputation. RESULTS: We performed 109 interventions in 78 consecutive patients with chronic peripheral artery stenoses and occlusions. The average age was 61.5+/-8.6 years and the majority were males (80%). Preinterventional angiography showed occlusions that involved the common iliac artery in 28 (36%) patients, the external iliac artery in 16 (21%) patients, internal iliac artery in 2 (3%) patients, and superficial femoral artery in 63 (81%) patients. Stenting was performed in half of the patients with a mean stent length of 69.6+/-50.3 mm. An average number of 1.24+/-0.55 stents was used for each lesion. During a mean follow-up of 18 months (range 4 to 42), there were 4 deaths, 3 MIs, 13 repeated percutaneous peripheral interventions due to restenosis in previously treated peripheral lesions, two urgent coronary interventions, two ischaemic strokes, two TIAs and one amputation. The combined follow--up MACCE end-point occurred in 32% of patients. CONCLUSIONS: Patients with concomitant CAD and PAD could safely undergo percutaneous cardiovascular and peripheral interventions. Multilevel intervention is associated with a promising long-term follow-up.     

The Shear Stress Determination in Tubular Specimens under Torsion in the Elastic–Plastic Strain Range from the Perspective of Fatigue Analysis

The comparison of shear stress determination methods in tubular specimens under torsion is presented in this paper. Four methods were analyzed: purely elastic solutions, purely plastic solutions, the midsection approach, and the Chaboche nonlinear kinematic hardening model. Using experimental data from self-designed and conducted fatigue experiments, an interesting insight on this problem was obtained that is not often tackled in the literature. It was shown that there are differences in determined shear stress values, and their level depends on a few factors. The midsection approach and purely plastic solution gave values of surface shear stress very close to the values obtained using the Chaboche nonlinear kinematic hardening model for high strain levels. The purely elastic solution gave proper results for the low strain ranges, close to the cyclic yield limit. Since none of the methods can be trusted in the full range of loading, an important conclusion from these analyses regards the formulated ranges of their applicability. It was also shown that the calculated values of shear stress and plastic and elastic strain energy density determined on this basis have a strong impact on fatigue life predictions. Finally, the influence of predicted values of shear stresses on the interpretation of cyclic hardening phenomena was also presented.     

Induction of immediate early genes expression in the mouse striatum following acute administration of synthetic cathinones

BackgroundSynthetic cathinones (SCs) form one of the most prominent group of the New Psychoactive Substances. SCs enhance central dopaminergic and noradrenergic neurotransmission, and are used as substitutes for illicit psychostimulants, namely cocaine, amphetamine, and methamphetamine. Changes in the expression of immediate early genes (IEGs) in the striatum underlie the addictive potential of drugs of abuse belonging to distinct pharmacologic groups. This work was aimed to assess the impact of acute administration of the prominent SCs on the mRNA levels of IEGs in the mouse striatum.MethodsEffects of 3,4-MDPV, 2,3-MDPV, α-PVP, PV8, PV9, methcathinone (MC) and 3-fluoromethcathinone (3-FMC) on the mRNA levels of ten IEGs, one and two hours after exposure, were measured in the mouse striatum using the quantitative RT-PCR technique.ResultsAll SCs used in the study produced increased mRNA levels of the following IEGs: Areg, c-fos, Csrnp1, Dusp1, Dusp14, Egr2, Egr4 and FosB. Additionally, the majority of SCs increased the expression of Homer1 and c-jun. The magnitude of observed changes varied by the drug, analyzed gene and, in many cases, by time after administration.ConclusionsThis study demonstrates that SCs increase the expression of IEGs in the mouse striatum, which may lead to a plethora of effects, as proteins encoded by the analyzed genes are involved in diverse actions, including an acute response to the drug and the neuroplasticity underlying the development of addiction.     

Quantifying the atomic-level mechanics of single long physisorbed molecular chains

Individual in situ polymerized fluorene chains 10–100 nm long linked by C–C bonds are pulled vertically from an Au(111) substrate by the tip of a low-temperature atomic force microscope. The conformation of the selected chains is imaged before and after manipulation using scanning tunneling microscopy. The measured force gradient shows strong and periodic variations that correspond to the step-by-step detachment of individual fluorene repeat units. These variations persist at constant intensity until the entire polymer is completely removed from the surface. Calculations based on an extended Frenkel–Kontorova model reproduce the periodicity and magnitude of these features and allow us to relate them to the detachment force and desorption energy of the repeat units. The adsorbed part of the polymer slides easily along the surface during the pulling process, leading to only small oscillations as a result of the high stiffness of the fluorenes and of their length mismatch with respect to the substrate surface structure. A significant lateral force also is caused by the sequential detachment of individual units. The gained insight into the molecule–surface interactions during sliding and pulling should aid the design of mechanoresponsive nanosystems and devices.Ever since the invention of the atomic force microscope (AFM) (1) and the first imaging applications, force spectroscopy has been applied to study the mechanical behavior of polymers (2); more complex chain-like biomolecules, e.g., DNA complementary strands (3); and proteins, subject to controlled extension (2) or applied force (4), mostly in solution and at room temperature. Reactive groups are chemically inserted at the ends and/or along each molecule to firmly bind some of them to suitably functionalized tips and sample surfaces. Irreversible jumps in curves of force vs. vertical separation may be associated in this way with the rupture of bonds or the unfolding of coiled subunits. If reproducible, the lowest peak in the histogram of the forces attained just before each jump is attributed to such an event in a single molecular chain or complementary pair. In the case of homogeneous polymers or protein segments, simulations based on two-state rate theory combined with a standard model of polymer nonlinear elasticity can reproduce such events, whereas reversible plateaus or continuous rises in the force may be associated with fast binding–rebinding processes or with large thermal fluctuations (2). Attention thus has focused on conformational changes strongly influenced by pulling speed or imposed force jumps (4) and also by external stimuli, e.g., optical excitation of inserted chromophores (5) or specific reactants or enzymes (6). Furthermore, mechanical forces recently were discovered by chemists as a unique stimulus to induce specific chemical reactions. In this so-called mechanochemistry, sonication typically is applied to polymer systems and is believed to result in a strong force acting on the weakest link in the chain, where the reaction takes place (7, 8). Regardless of the direct or indirect exposure to force, it is clear that the mechanics of polymer chains constrained in their surrounding environment is of utmost importance for a variety of biophysical and chemical processes as well as self-healing materials applications (9, 10).A few pulling studies have been conducted on polyelectrolytes unspecifically adsorbed on self-assembled monolayers via tunable electrostatic interactions (11), including DNA (12). They merely revealed noisy force plateaus, interpreted as continuous partial desorption of single chains, terminated by a drop to zero upon complete detachment from the surface. Despite the undisputed merit of these studies, little is known about the mechanical behavior of single molecular chains pulled off a surface, both defined and characterized on the atomic scale, in the absence of significant thermal fluctuations and drifts. Measurements at low temperature reduce the diffusion of adsorbates and provide an opportunity to determine the energetic landscape of specific molecules interacting with a surface under controlled conditions. As demonstrated here, the sliding and detachment mechanisms of individual polymer repeat units can then be inferred from the analysis of pulling experiments. A detailed interpretation of our results, based on a modified Frenkel–Kontorova (FK) model (13), also is presented.