Ambulatory blood pressure monitoring in clinical trials with antihypertensive agents

Ambulatory blood pressure monitoring (ABPM) is being used increasingly for the evaluation of antihypertensive agents in clinical trials. In this brief review several aspects of ABPM are discussed. In particular, attention is paid to the extent to which ABPM is subject to a placebo response and the extent to which the sample size of the study population can be reduced with this type of measurement. In addition, some remarks are made with regard to how selection of patients with this methodology can be improved and how it may be used as a tool to evaluate the duration of action of antihypertensive agents. Finally, some potential disadvantages of ABPM as compared to conventional clinic blood pressure measurements are discussed

Recent advances in hypertension and cardiovascular toxicities with vascular endothelial growth factor inhibition

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Phase transition and spin-wave dispersion in quantum Hall bilayers at filling factor nu=1

We present an effective Hamiltonian for a bilayer quantum Hall system at filling factor $\nu=1$ neglecting charge fluctuations. Our model is formulated in terms of spin and pseudospin operators and is an exact representation of the system within the above approximation. We analyze its low-lying excitations in terms of spin-wave theory. Moreover we add to previous first-principle exact-diagonalization studies concentrating on the quantum phase transition seen in this system.Comment: Four pages, proceedings for EP2DS-14, Prague 200

Consistent Batalin--Fradkin quantization of Infinitely Reducible First Class Constraints

We reconsider the problem of BRST quantization of a mechanics with infinitely reducible first class constraints. Following an earlier recipe [Phys. Lett. B 381, 105, (1996)], the original phase space is extended by purely auxiliary variables, the constraint set in the enlarged space being first stage of reducibility. The BRST charge involving only a finite number of ghost variables is explicitly constructed.Comment: 5 pages, LaTex. Minor corrections including the title. The version to appear in Phys. Rev.

Semicarbazide-sensitive amine oxidase (SSAO): from cell to circulation

Semicarbazide-sensitive amine oxidase (SSAO) is a multi-functional enzyme widely present in nature. It converts primary amines into their corresponding aldehydes, while generating H(2)O(2) and NH(3). In mammals, SSAO circulates in plasma, while a membrane-bound form (often referred to as vascular adhesion protein-1, VAP-1) is found in many tissues and organs, especially in adipocytes and vascular endothelial and smooth muscle cells. In recent years, evidence has been accumulating that SSAO has a role in protein cross-linking, formation of advanced glycation end-products, atherogenesis, glucose regulation and leukocyte extravasation at inflammation sites. Plasma SSAO is quite stable in healthy adults, but is elevated in diabetes mellitus (both type 1 and type 2), congestive heart failure and liver cirrhosis. The origin of circulating SSAO remains unclear, but recent evidence from clinical studies and from (transgenic) animal studies suggests that adipocytes and vascular endothelial cells may be the most important source. Studies with cell cultures show evidence that the membrane-bound SSAO can be split off from the cells, thus giving rise to the (truncated) circulating form of SSAO. In some pathological conditions the diseased organ may be the main source of the elevated plasma SSAO. Little is known as yet about the regulation of plasma SSAO. Thyroid hormone appears to play a (modest) role in this respect. Further evidence from clinical, animal and cell-culture studies, helped by the new availability of selective SSAO inhibitors, is needed to shed more light on the question of the regulation of SSAO

Hypertension: Renin-Angiotensin-Aldosterone System Alterations

Blockers of the renin-angiotensin-aldosterone system (RAAS), that is, renin inhibitors, angiotensin (Ang)-converting enzyme (ACE) inhibitors, Ang II type 1 receptor antagonists, and mineralocorticoid receptor antagonists, are a cornerstone in the treatment of hypertension. How exactly they exert their effect, in particular in patients with low circulating RAAS activity, also taking into consideration the so-called Ang II/aldosterone escape that often occurs after initial blockade, is still incompletely understood. Multiple studies have tried to find parameters that predict the response to RAAS blockade, allowing a personalized treatment approach. Consequently, the question should now be answered on what basis (eg, sex, ethnicity, age, salt intake, baseline renin, ACE or aldosterone, and genetic variance) a RAAS blocker can be chosen to treat an individual patient. Are all blockers equal? Does optimal blockade imply maximum RAAS blockade, for example, by combining ≥2 RAAS blockers or by simply increasing the dose of 1 blocker? Exciting recent investigations reveal a range of unanticipated extrarenal effects of aldosterone, as well as a detailed insight in the genetic causes of primary aldosteronism, and mineralocorticoid receptor blockers have now become an important treatment option for resistant hypertension. Finally, apart from the deleterious ACE-Ang II-Ang II type 1 receptor arm, animal studies support the existence of protective aminopeptidase A-Ang III-Ang II type 2 receptor and ACE2-Ang-(1 to 7)-Mas receptor arms, paving the way for multiple new treatment options. This review provides an update about all these aspects, critically discussing the many controversies and allowing the reader to obtain a full understanding of what we currently know about RAAS alterations in hypertension

Drug mechanisms to help in managing resistant hypertension in obesity

Obesity is a major risk factor for the development of hypertension. Because the prevalence of obesity is increasing worldwide, the prevalence of obesity hypertension is also increasing. Importantly, hypertension in obesity is commonly complicated by dyslipidemia and type 2 diabetes mellitus and hence imposes a high cardiovascular disease risk. Furthermore, obesity is strongly associated with resistant hypertension. Activation of the sympathetic nervous system and the renin-angiotensin system, leading to renal sodium and water retention, links obesity with hypertension. There is also evidence for the release of factors by visceral adipose tissue promoting excessive aldosterone production, and a more central role of aldosterone in obesity hypertension is emerging. Randomized studies evaluating the effect of different classes of antihypertensive agents in obesity hypertension are scarce, short-lasting, and small. Considering the emerging role of aldosterone in the pathogenesis of obesity hypertension, mineralocorticoid receptor antagonism may play a more central role in the pharmacologic treatment of obesity hypertension in the near future

Dynamics of Quark-Gluon-Plasma Instabilities in Discretized Hard-Loop Approximation

Non-Abelian plasma instabilities have been proposed as a possible explanation for fast isotropization of the quark-gluon plasma produced in relativistic heavy-ion collisions. We study the real-time evolution of these instabilities in non-Abelian plasmas with a momentum-space anisotropy using a hard-loop effective theory that is discretized in the velocities of hard particles. We extend our previous results on the evolution of the most unstable modes, which are constant in directions transverse to the direction of anisotropy, from gauge group SU(2) to SU(3). We also present first full 3+1-dimensional simulation results based on velocity-discretized hard loops. In contrast to the effectively 1+1-dimensional transversely constant modes we find subexponential behaviour at late times.Comment: 30 pages, 16 figures. v3 typos fixe