A current evaluation of the safety of angiotensin receptor blockers and direct renin inhibitors

The safety of angiotensin II receptor blockers (ARBs) for the treatment of hypertension and cardiovascular and renal diseases has been well documented in numerous randomized clinical trials involving thousands of patients. However, recent concerns have surfaced about possible links between ARBs and increased risks of myocardial infarction and cancer. Less is known about the safety of the direct renin inhibitor aliskiren, which was approved as an antihypertensive in 2007. This article provides a detailed review of the safety of ARBs and aliskiren, with an emphasis on the risks of cancer and myocardial infarction associated with ARBs. Safety data were identified by searching PubMed and Food and Drug Administration (FDA) Web sites through April 2011. ARBs are generally well tolerated, with no known class-specific adverse events. The possibility of an increased risk of myocardial infarction associated with ARBs was suggested predominantly because the Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial reported a statistically significant increase in the incidence of myocardial infarction with valsartan compared with amlodipine. However, no large-scale, randomized clinical trials published after the VALUE study have shown a statistically significant increase in the incidence of myocardial infarction associated with ARBs compared with placebo or non-ARBs. Meta-analyses examining the risk of cancer associated with ARBs have produced conflicting results, most likely due to the inherent limitations of analyzing heterogeneous data and a lack of published cancer data. An ongoing safety investigation by the FDA has not concluded that ARBs increase the risk of cancer. Pooled safety results from clinical trials indicate that aliskiren is well tolerated, with a safety profile similar to that of placebo. ARBs and aliskiren are well tolerated in patients with hypertension and certain cardiovascular and renal conditions; their benefits outweigh possible safety concerns

Kinetic Simulation of He radio frequency capacitive coupled plasma

Radiofrequency capacitively coupled plasma is studied theoretically using a Particle-in-Cell code. For He discharge, the time-averaged sheaths are in the range of few centimeters. The sheath potential, ion, and electron energy and angular distributions, discharge current, and dissipated power depend on the driven potentials and frequencies. Increasing the amplitude of the high radio frequencies increases the bulk density and the sheath potential and, consequently, increases the plasma processing rate. Increasing the intermediate radio frequency amplitude allows a wider sheath with a broad ion energy distribution and a narrower ion angular distribution. Changing the amplitude and the phase shift between driven frequencies provide different energies and angular distribution allowing performing various processes. The interplay between the sheath and bulk dynamics in the intermediate radiofrequency regime and the high-frequency regime may excite harmonics in the discharge current

Quantifying Dynamic Balance in Young, Elderly and Parkinson's Individuals: A Systematic Review

Introduction: Falling is one of the primary concerns for people with Parkinson's Disease and occurs predominately during dynamic movements, such as walking. Several methods have been proposed to quantify dynamic balance and to assess fall risk. However, no consensus has been reached concerning which method is most appropriate for examining walking balance during unperturbed and perturbed conditions, particularly in Parkinson's Disease individuals. Therefore, this systematic review aimed to assess the current literature on quantifying dynamic balance in healthy young, elderly and Parkinson's individuals during unperturbed and perturbed walking.Methods: The PubMed database was searched by title and abstract for publications quantifying dynamic balance during unperturbed and mechanically perturbed walking conditions in elderly adults and PD. Inclusion criteria required publications to be published in English, be available in full-text, and implement a dynamic balance quantification method. Exclusion criteria included clinical dynamic balance measures, non-mechanical perturbations, pathologies other than PD, and dual-tasking conditions. The initial database search yielded 280 articles, however, only 81 articles were included after title, abstract and full-text screening. Methodological quality and data were extracted from publications included in the final synthesis.Results: The dynamic balance articles included 26 Coefficient of Variation of Spatiotemporal Variability, 10 Detrended Fluctuation Analysis, 20 Lyapunov Exponent, 7 Maximum Floquet Multipliers, 17 Extrapolated Center of Mass, 11 Harmonic Ratios, 4 Center of Mass-Center of Pressure Separation, 2 Gait Stability Ratio, 1 Entropy, 3 Spatiotemporal Variables, 2 Center of Gravity and Center of Pressure, and 2 Root Mean Square in the final synthesis. Assessment of methodological quality determined that 58 articles had a low methodological rating, a 22 moderate rating, and 1 having a high rating.Conclusion: Careful consideration must be given when selecting a method to quantify dynamic balance because each method defines balance differently, reflects a unique aspect of neuromuscular stability mechanisms, and is dependent on the walking condition (unperturbed vs. perturbed). Therefore, each method provides distinct information into stability impairment in elderly and PD individuals

Case-Based Study: From Prediabetes to Complications—Opportunities for Prevention

A 31-year-old man presents with central obesity, hypertension, and abnormal lipids. How would you manage this patient

Receptor-Induced Dilatation in the Systemic and Intrarenal Adaptation to Pregnancy in Rats

Normal pregnancy is associated with systemic and intrarenal vasodilatation resulting in an increased glomerular filtration rate. This adaptive response occurs in spite of elevated circulating levels of angiotensin II (Ang II). In the present study, we evaluated the potential mechanisms responsible for this adaptation. The reactivity of the mesangial cells (MCs) cultured from 14-day-pregnant rats to Ang II was measured through changes in the intracellular calcium concentration ([Cai]). The expression levels of inducible nitric oxide synthase (iNOS), the Ang II-induced vasodilatation receptor AT2, and the relaxin (LGR7) receptor were evaluated in cultured MCs and in the aorta, renal artery and kidney cortex by real time-PCR. The intrarenal distribution of LGR7 was further analyzed by immunohistochemistry. The MCs displayed a relative insensitivity to Ang II, which was paralleled by an impressive increase in the expression level of iNOS, AT2 and LGR7. These results suggest that the MCs also adapt to the pregnancy, thereby contributing to the maintenance of the glomerular surface area even in the presence of high levels of Ang II. The mRNA expression levels of AT2 and LGR7 also increased in the aorta, renal artery and kidney of the pregnant animals, whereas the expression of the AT1 did not significantly change. This further suggests a role of these vasodilatation-induced receptors in the systemic and intrarenal adaptation during pregnancy. LGR7 was localized in the glomeruli and on the apical membrane of the tubular cells, with stronger labeling in the kidneys of pregnant rats. These results suggest a role of iNOS, AT2, and LGR7 in the systemic vasodilatation and intrarenal adaptation to pregnancy and also suggest a pivotal role for relaxin in the tubular function during gestation

Plasma renin activity and aldosterone concentrations in hypertensive cats with and without azotemia and in response to treatment with amlodipine besylate

BACKGROUND: Role of renin‐angiotensin aldosterone system (RAAS) in feline systemic hypertension is poorly understood. OBJECTIVES: Examine plasma renin activity (PRA) and plasma aldosterone concentrations (PAC) in normotensive and hypertensive cats with variable renal function and in response to antihypertensive therapy. ANIMALS: One hundred and ninety‐six cats >9 years from first opinion practice. METHODS: PRA, PAC, and aldosterone‐to‐renin ratio (ARR) were evaluated in cats recruited prospectively and grouped according to systolic blood pressure (SBP) and renal function (nonazotemic normotensive [Non‐Azo‐NT], nonazotemic hypertensive [Non‐Azo‐HT], azotemic normotensive [Azo‐NT], azotemic hypertensive [Azo‐HT]). Changes in PRA and PAC were evaluated with antihypertensive therapy (amlodipine besylate). RESULTS: Plasma renin activity (ng/mL/h; P = .0013), PAC (pg/mL; P < .001), and ARR (P = 0.0062) differed significantly among groups. PRA (ng/mL/h) was significantly lower in hypertensive (Non‐Azo‐HT; n = 25, median 0.22 [25th percentile 0.09, 75th percentile 0.39], Azo‐HT; n = 44, 0.33 [0.15, 0.48]) compared with Non‐Azo‐NT cats (n = 57, 0.52 [0.28, 1.02]). Azo‐HT cats had significantly higher PAC (n = 22, 149.8 [103.1, 228.7]) than normotensive cats (Non‐Azo‐NT; n = 26, 45.4 [19.6, 65.0], Azo‐NT; n = 18, 84.1 [38.6, 137.8]). ARR was significantly higher in Azo‐HT (n = 20, 503.8 [298.8, 1511]) than Azo‐NT cats (n = 16, 97.8 [77.0, 496.4]). Significant increase in PRA was documented with antihypertensive therapy (pretreatment [n = 20] 0.32 [0.15–0.46], posttreatment 0.54 [0.28, 1.51]), but PAC did not change. CONCLUSIONS AND CLINICAL IMPORTANCE: Hypertensive cats demonstrate significantly increased PAC with decreased PRA. PRA significantly increases with antihypertensive therapy. Additional work is required to determine the role of plasma aldosterone concentration in the pathogenesis of hypertension and whether this relates to autonomous production or activation of RAAS without demonstrable increase in PRA

Endothelial Dysfunction in Human Essential Hypertension

Although the endothelium has a number of important functions, the term endothelial dysfunction is commonly used to describe impairment in its vasodilatory capacity. It is increasingly recognized that this is related to hypertension, although whether it predates essential hypertension or is a consequence of it is still unknown. In this review, we explore the mechanisms of endothelial dysfunction in essential hypertension, its prognostic significance and methods of pharmacological reversal

Mechanisms of progression of chronic kidney disease

Chronic kidney disease (CKD) occurs in all age groups, including children. Regardless of the underlying cause, CKD is characterized by progressive scarring that ultimately affects all structures of the kidney. The relentless progression of CKD is postulated to result from a self-perpetuating vicious cycle of fibrosis activated after initial injury. We will review possible mechanisms of progressive renal damage, including systemic and glomerular hypertension, various cytokines and growth factors, with special emphasis on the renin–angiotensin–aldosterone system (RAAS), podocyte loss, dyslipidemia and proteinuria. We will also discuss possible specific mechanisms of tubulointerstitial fibrosis that are not dependent on glomerulosclerosis, and possible underlying predispositions for CKD, such as genetic factors and low nephron number