As suggested by its American brand name (Sensipar), the calcimimetic cinacalcet sensitizes the parathyroid cells to the extracellular calcium signal, suppressing parathyroid hormone (PTH) release and synthesis and preventing parathyroid cell proliferation. This primary PTH suppression decreases the release of calcium and phosphate from bone without increasing intestinal absorption of calcium and phosphate. Therefore cinacalcet decreases the risk of hypercalcemia and hyperphosphatemia in contrast to 1alpha-OH vitamin D derivatives. Compared with calcium-containing oral phosphate binder (OPB), it increases the risk of hypocalcemia and may decrease the PTH-mediated phosphaturia in predialysis patients. This justifies its combined use with calcium-containing OPB in order to prevent hypocalcemia and enhance the hypophosphatemic effect of the latter, while improving PTH suppression. The National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI) has recommended restriction of supplemental elemental calcium to 1.5 g/day, a recommendation that we believe should be revised. No pathophysiologic or randomized trial data have yet evidenced the absolute necessity for systematically using 1alpha-OH vitamin D derivatives and noncalcium-containing OPB rather than higher doses of calcium-containing OPB alone in uremic patients without vitamin D insufficiency. In patients with hyperparathyroidism as severe as in the "Treat to Goal Study," the Durham study showed that a calcium carbonate dose more than three times the K/DOQI limit could decrease PTH into the recommended range, with the advantage of a lower calcium-phosphate product compared with the combination of calcitriol and noncalcium OPB. Besides the efficient PTH suppression associated with lower calcium-phosphate product and a good gastrointestinal tolerance, long-term data suggest that cinacalcet may decrease the risk of parathyroidectomy and fracture, while high bone turnover lesions are improved. However, no long-term data on bone mineral density and cardiovascular calcification and complications are yet available. Such studies, along with those comparing cinacalcet and 1alpha-OH vitamin D-based approaches to hyperparathyroidism, are needed.
To study processes related to weightlessness in ground-based cell biological research, a microgravity environment is typically simulated with a clinostat - a small laboratory device that rotates cell culture vessels with the aim to average-out the vector of gravitational forces. Here, we report that these rotational movements induce complex fluid motions in the cell culture vessel that can trigger unintended cellular responses. Specifically, we demonstrate that suppression of myotube formation by 2D-clino-rotation is not an effect of a theoretically assumed microgravity but instead is a consequence of fluid motion. Therefore, cell biological results from clino-rotation cannot be attributed to microgravity unless alternative explanations have been rigorously tested and ruled out. In this setting we consider the inclusion of at least two control experiments as mandatory, i) a static, non-rotating control, and ii) a control for fluid motion. Finally, we discuss strategies to minimize spurious fluid motion in clino-rotation experiments.
In his commentary on the VALUE trial [1,2], Williams [3] proposes to end the debate about the possibility of antihypertensive drugs exerting cardiovascular benefits additional to those due to blood pressure reduction, and claims they do not exist. We believe that this is an overstatement, and the concept may not be true at least when organ-specific outcomes and specific populations are considered.Admittedly, the meta-analysis made by the Blood Pressure Lowering Treatment Trialists' Collaboration [4] showed that, when angiotensin-converting enzyme-inhibitors (ACEI) and calcium antagonists were compared between them or with conventional treatment (thiazides and/or beta-blockers), total and cardiovascular mortality, as well as the risk for major cardiovascular events and myocardial infarction, were strictly comparable. However, when stroke and heart failure were considered, significant (and opposite) differences could be found: stroke risk was higher with ACEIs (12% and significant versus calcium antagonists, 9% and only borderline significant versus conventional treatment) whereas, by contrast, heart failure risk was significantly higher with calcium antagonists than with ACEI (22%) or convential treatment (33%).This less than optimal prevention of heart failure with calcium antagonists is even more remarkable because the blood pressure reduction was greater with this class of drugs compared to ACEIs [2]. As noted by Staessen and Birkenhäger [5] in their commentary on the VALUE papers, the limited preventive action of calcium antagonists on heart failure might be explained by their negative inotropic action on the myocardium. In VALUE, the superiority of valsartan over amlodipine could not be fully demonstrated, because of the 2.2 mmHg higher systolic blood pressure achieved in valsartan compared to amlodipine patients, but a comparison of patients with systolic blood pressure values matched at 6 months, as performed by the VALUE authors [2], suggests that valsartan may protect against heart failure better than amlodipine, with the estimated relative risk (RR) being significantly lower (RR ¼ 0.81; 95% confidence interval 0.66-0.99; P ¼ 0.04). In the same population with systolic blood pressure values matched at 6 months, myocardial infarction risk was comparable (RR ¼ 0.97), and therefore the idea that the difference in heart failure risk is secondary to a difference in coronary risk can be excluded.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.