The Role of Ivabradine in the Management of Angina Pectoris

Stable angina pectoris affects 2–4 % of the population in Western countries and entails an annual risk of death and nonfatal myocardial infarction of 1–2 % and 3 %, respectively. Heart rate (HR) is linearly related to myocardial oxygen consumption and coronary blood flow, both at rest and during stress. HR reduction is a key target for the prevention of ischemia/angina and is an important mechanism of action of drugs which are recommended as first line therapy for the treatment of angina in clinical guidelines. However, many patients are often unable to tolerate the doses of beta blocker or non-dihydropyridine calcium antagonists required to achieve the desired symptom control. The selective pacemaker current inhibitor ivabradine was developed as a drug for the management of patients with angina pectoris, through its ability to reduce HR specifically. The available data suggest that ivabradine is a well-tolerated and effective anti-anginal agent and it is recommended as a second-line agent for relief of angina in guidelines. However, recent clinical trials of ivabradine have failed to show prognostic benefit and have raised potential concerns about safety. This article will review the available evidence base for the current role of ivabradine in the management of patients with symptomatic angina pectoris in the context of stable coronary artery disease

Effective Average Action of Chern-Simons Field Theory

The renormalization of the Chern-Simons parameter is investigated by using an exact and manifestly gauge invariant evolution equation for the scale-dependent effective average action.Comment: 14 pages, late

Chern-Simons as a geometrical set up for three dimensional gauge theories

Three dimensional Yang-Mills gauge theories in the presence of the Chern-Simons action are seen as being generated by the pure topological Chern-Simons term through nonlinear covariant redefinitions of the gauge fieldComment: 26 pages, latex2

Infrared-Finite Amplitudes for Massless Gauge Theories

We present a method to construct infrared-finite amplitudes for gauge theories with massless fermions. Rather than computing $S$-matrix elements between usual states of the Fock space we construct order-by-order in perturbation theory dressed states that incorporate all long-range interactions. The $S$-matrix elements between these states are shown to be free from soft and collinear singularities. As an explicit example we consider the process $e^+ e^-\to 2$ jets at next-to-leading order in the strong coupling. We verify by explicit calculation that the amplitudes are infrared finite and recover the well-known result for the total cross section $e^+ e^-\to$ hadrons.Comment: 46 page

Physically meaningful and not so meaningful symmetries in Chern-Simons theory

We explicitly show that the Landau gauge supersymmetry of Chern-Simons theory does not have any physical significance. In fact, the difference between an effective action both BRS invariant and Landau supersymmetric and an effective action only BRS invariant is a finite field redefinition. Having established this, we use a BRS invariant regulator that defines CS theory as the large mass limit of topologically massive Yang-Mills theory to discuss the shift k \to k+\cv of the bare Chern-Simons parameter $k$ in conncection with the Landau supersymmetry. Finally, to convince ourselves that the shift above is not an accident of our regularization method, we comment on the fact that all BRS invariant regulators used as yet yield the same value for the shift.Comment: phyzzx, 21 pages, 2 figures in one PS fil

Renormalization Ambiguities in Chern-Simons Theory

We introduce a new family of gauge invariant regularizations of Chern-Simons theories which generate one-loop renormalizations of the coupling constant of the form $k\to k+2 s c_v$ where $s$ can take any arbitrary integer value. In the particular case $s=0$ we get an explicit example of a gauge invariant regularization which does not generate radiative corrections to the bare coupling constant. This ambiguity in the radiative corrections to $k$ is reminiscent of the Coste-L\"uscher results for the parity anomaly in (2+1) fermionic effective actions.Comment: 10 pages, harvmac, no changes, 1 Postscript figure (now included

Differential Regularization of Topologically Massive Yang-Mills Theory and Chern-Simons Theory

We apply differential renormalization method to the study of three-dimensional topologically massive Yang-Mills and Chern-Simons theories. The method is especially suitable for such theories as it avoids the need for dimensional continuation of three-dimensional antisymmetric tensor and the Feynman rules for three-dimensional theories in coordinate space are relatively simple. The calculus involved is still lengthy but not as difficult as other existing methods of calculation. We compute one-loop propagators and vertices and derive the one-loop local effective action for topologically massive Yang-Mills theory. We then consider Chern-Simons field theory as the large mass limit of topologically massive Yang-Mills theory and show that this leads to the famous shift in the parameter $k$. Some useful formulas for the calculus of differential renormalization of three-dimensional field theories are given in an Appendix.Comment: 25 pages, 4 figures. Several typewritten errors and inappropriate arguments are corrected, especially the correct adresses of authors are give

A case report of accidental intoxication following ingestion of foxglove confused with borage : high digoxinemia without major complications

Foxglove (Digitalis purpurea L.) leaves are frequently confused with borage (Borago officinalis L.), which is traditionally used as a food ingredient. Due to the presence of the cardiac glycosides, mostly digitoxin, foxglove leaves are poisonous to human and may be fatal if ingested. A 55-year-old Caucasian woman complaining weakness, fatigue, nausea, and vomiting was admitted to the Emergency Department. Her symptoms started following consumption of a home-made savory pie with 5 leaves from a plant bought in a garden nursery as borage. Digoxinemia was high (10.4\u2009\u3bcg/L). The patient was admitted to the cardiac intensive care unit for electrocardiographic monitoring. Two days after admission, a single episode of advanced atrioventricular (AV) block was recorded by telemetry, followed by a second-degree AV block episode. Plasma samples at day 11 were analysed by LC-MS spectrometry, and gitoxin was identified suggesting that this compound may be responsible for the clinical toxicity rather than digoxin. In the case of Digitalis spp. poisoning, laboratory data should be interpreted according to the clinical picture and method of analysis used since a variety of glycosides, which are chemically similar to the cardioactive glycosides but without or with fewer cardiac effects, may be incorrectly recognized as digoxin by the test, giving misleading results

The Chern-Simons Coefficient in Supersymmetric Non-abelian Chern-Simons Higgs Theories

By taking into account the effect of the would be Chern-Simons term, we calculate the quantum correction to the Chern-Simons coefficient in supersymmetric Chern-Simons Higgs theories with matter fields in the fundamental representation of SU(n). Because of supersymmetry, the corrections in the symmetric and Higgs phases are identical. In particular, the correction is vanishing for N=3 supersymmetric Chern-Simons Higgs theories. The result should be quite general, and have important implication for the more interesting case when the Higgs is in the adjoint representation.Comment: more references and explanation about rgularization dpendence are included, 13 pages, 1 figure, latex with revte

Schwann Cell Autocrine and Paracrine Regulatory Mechanisms, Mediated by Allopregnanolone and BDNF, Modulate PKCε in Peripheral Sensory Neurons

Protein kinase type C-\u3b5 (PKC\u3b5) plays important roles in the sensitization of primary afferent nociceptors, such as ion channel phosphorylation, that in turn promotes mechanical hyperalgesia and pain chronification. In these neurons, PKC\u3b5 is modulated through the local release of mediators by the surrounding Schwann cells (SCs). The progesterone metabolite allopregnanolone (ALLO) is endogenously synthesized by SCs, whereas it has proven to be a crucial mediator of neuron-glia interaction in peripheral nerve fibers. Biomolecular and pharmacological studies on rat primary SCs and dorsal root ganglia (DRG) neuronal cultures were aimed at investigating the hypothesis that ALLO modulates neuronal PKC\u3b5, playing a role in peripheral nociception. We found that SCs tonically release ALLO, which, in turn, autocrinally upregulated the synthesis of the growth factor brain-derived neurotrophic factor (BDNF). Subsequently, glial BDNF paracrinally activates PKC\u3b5 via trkB in DRG sensory neurons. Herein, we report a novel mechanism of SCs-neuron cross-talk in the peripheral nervous system, highlighting a key role of ALLO and BDNF in nociceptor sensitization. These findings emphasize promising targets for inhibiting the development and chronification of neuropathic pain