Why Does Obesity Lead to Hypertension? Further Lessons from the Intersalt Study.

Objectives To analyze correlations between major determinants of blood pressure (BP), in efforts to generate and compare predictive models that explain for variance in systolic, diastolic, and mean BP amongst participants of the Intersalt study. Methods Data from the Intersalt study, consisting of nearly 10,000 subjects from 32 different countries, were reviewed and analyzed. Published mean values of 24 hour urinary electrolyte excretion (Na+, K+), 24 hour urine creatinine excretion, body mass index (BMI, kg/m^2), and blood pressure data were extracted and imported into Matlab™ for stepwise linear regression analysis. Results As shown earlier, strong correlations between urinary sodium excretion (UNaV) and systolic, diastolic and mean blood pressure were noted as well as between UNaV and the age dependent increase in systolic blood pressure. Of interest, BMI and urinary creatinine excretion rate (UCrV) also both correlated with systolic blood pressure, but the ratio of BMI/UCrV, constructed to be a measure of obesity, correlated negatively with systolic blood pressure. Conclusions Our results offer population-based evidence suggesting that increased size due to muscle mass rather than adiposity may correspond more to blood pressure. Additional data bases will need to be sampled and analyzed to further validate these observations

DPCM: a method for modelling and analysing design process changes based on the Applied Signposting Model

Research on changes in design has focused on changes in the product domain. However, because the product's design process may change as well, this article suggests a comprehensive method to support modelling and analysing changes in the process domain (DPCs). After developing the concept for the Design Process Change Method (DPCM) based on requirements derived from literature and industrial practice, the DPCM is detailed and computationally implemented using the framework of the Applied Signposting Model. The DPCM enables design teams to conduct various useful analyses, which enhance the understanding of DPC effects on process performance, support process execution through suggesting reactions to DPCs, and support process planning through identifying and prioritising the ‘right’ DPCs. The method’s application is demonstrated based on the fan sub-system preliminary design process of Rolls-Royce PLC.This work was funded by Innovate UK/Technology Strategy Board and Rolls-Royce PL

The physiological and clinical importance of sodium potassium ATPase in cardiovascular diseases

The Na/K-ATPase has been extensively studied, but it is only recently that its role as a scaffolding and signaling protein has been identified. It has been identified that cardiotonic steroids (CTS) such as digitalis mediate signal transduction through the Na/K-ATPase in a process found to result in the generation of reactive oxygen species (ROS). As these ROS also appear capable of initiating this signal cascade, a feed forward amplification process has been postulated and subsequently implicated in some disease pathways including uremic cardiomyopathy

Na/K-ATPase amplification of oxidant stress; a universal but unrecognized clinical target?

The Na/K-ATPase has a signaling function which appears to be separate from its ion pumping function. This signaling function refers to the transduction of conformational changes in the Na/K-ATPase alpha1 subunit into activating Src’s tyrosine kinase activity, triggering a cascade which generates reactive oxygen species (ROS), modulates other signaling pathways, and causes many physiological and pathophysiological effects. We have recently observed that ROS themselves as well as cardiotonic steroids can actually initiate the signal by directly inducing conformational changes in alpha1. It therefore appears that the Na/K-ATPase signal cascade can serve as a feed forward amplification for ROS with circulating cardiotonic steroids setting the gain. Work in both cellular and animal models of disease suggest that this amplification process is activated in conditions characterized by oxidant stress ranging from cancer to obesity/metabolic syndrome and may serve as a potential clinical target for interventions

Alkali Therapy in Lactic Acidosis

This report attempts to frame the debate about clinical administration of sodium bicarbonate in the setting of lactic acidosis in terms of simple questions. Specifically, we address why we develop lactic acidosis in some circumstances, how acute lactic acidosis impairs cardiovascular function and why sodium bicarbonate may have deleterious effects which limit its utility. We also attempt to explore treatment alternatives to sodium bicarbonate

The Role of Na/K-ATPase Signaling in Oxidative Stress Related to Obesity and Cardiovascular Disease

Na/K-ATPase has been extensively studied for its ion pumping function, but, in the past several decades, has been identified as a scaffolding and signaling protein. Initially it was found that cardiotonic steroids (CTS) mediate signal transduction through the Na/K-ATPase and result in the generation of reactive oxygen species (ROS), which are also capable of initiating the signal cascade. However, in recent years, this Na/K-ATPase/ROS amplification loop has demonstrated significance in oxidative stress related disease states, including obesity, atherosclerosis, heart failure, uremic cardiomyopathy, and hypertension. The discovery of this novel oxidative stress signaling pathway, holds significant therapeuti

Dashing away hypertension: Evaluating the efficacy of the dietary approaches to stop hypertension diet in controlling high blood pressure

The dietary approaches to stop hypertension (DASH) diet has been developed and popularized as a non-pharmaceutical intervention for high blood pressure reduction since 1995. However, to date, a comprehensive description of the biochemical rationale behind the diet’s principal guidelines has yet to be compiled. With rising interest for healthy and reliable life-style modifications to combat cardiovascular disease, this review aims to compile the most recent and relevant studies on this topic and make an informed assessment as to the efficacy of and underlying mechanisms operant in the DASH diet. Specifically, the merits of lowering dietary intake of sodium and saturated fat, as well as increasing the intake of fruits, vegetables, fiber, and dairy, have been shown to attenuate hypertension individually. Upon review of this evidence, we conclude that the combination of dietary patterns proposed in the DASH diet is effective in attenuating high blood pressure. We also suggest that efforts to more widely implement adoption of the DASH diet would be beneficial to public health

From LCME probation to compliance: the Marshall University Joan C Edwards School of Medicine experience

The Joan C Edwards School of Medicine (Marshall University, Huntington, WV, USA) was placed on probation by the Liaison Committee on Medical Education (LCME) in June 2011. In the following 2 years, extensive changes were made to address the numerous citations that resulted in this probation. In October 2013, the LCME lifted probation. In this article, we detail the challenges and solutions identified relevant to our struggle with compliance

Use of Surface-Enhanced Laser Desorption/Ionization with Time of Flight (SELDI-TOF) of the Urine in the Assessment of Acute Kidney Injury (AKI)

Background: Urinalysis is an important component in the assessment of acute kidney injury (AKI). Proteonomics is a rapidly developing approach in the analysis of physiological states. Several techniques have been developed to screen for protein populations. In this regard SELDI-TOF is a technique based on mass spectroscopy that is being utilized in proteonomics research. Methods:For this study, clean catch or catheterized urine was collected from normals (n=18) and patients referred to the renal service with AKI. Based upon urine and serum chemistries, clinical parameters, and microscopic urinalysis, the urines were separated into those consistent with prerenal azotemia (n=17) and acute tubular necrosis (ATN) (n=29). Initially, 5 samples each were chosen from the pre-renal and ATN who had no preexisting renal disease. Other etiologies of AKI were not included in this analysis. The urine specimens were diluted 1:5 and deposited onto an H4 ProteinChip array using 50% acetonitrile as the binding buffer. This system captured the greatest spectral range with the SELDI-TOF evaluation (compared to SAX, WCX2, IMAC, and NP1 ProteinChips). Low (250) and high (300) laser intensities were utilized to ionize and desorb the protein molecules; the spectra were collected in a positive ion mode and analyzed with Ciphergen Peaks software (v 3.0). Results: Five peaks with the high laser power were identified as potential candidates to discriminate between AKI due to prerenal or ATN causes. Those urines from the prerenal subjects were associated with detectable masses at 22.6 and 44.8 kilodaltons (KD); whereas subjects with ATN were noted to have urine with substantial masses at 11, 11.7, and 14.6 KD. The intensity of these peaks were then added together and normalized with the individual components of the discriminate peaks representing a percentage of the total. The prerenal and ATN subjects were then randomized in a training set consisting of 23 subjects and a testing set consisting of 23 subjects. Multiple linear regression was performed on the training set, and this allowed for 65% accuracy when applied to the testing set. Feed forward neural networks with hidden neuron layers ranging from 2-10 achieved similar predictive capability on the training set and testing sets. Conclusions: Although the SELDI-TOF methodology may be a useful adjunct in the assessment of AKI and renal disease, we suggest that larger training sets will be necessary to effectively exploit this strategy