Adrenergic modulation of potassium metabolism in uremia

Adrenergic modulation of potassium metabolism in uremia. The effect of chronic beta adrenergic blockade on potassium homeostasis during moderate intensity exercise (40% of VO2 max) was examined in seven end-stage renal patients who were being maintained on chronic dialysis treatment. Subjects participated in three study protocols: 1) exercise alone, 2) exercise plus propranolol (a nonselective beta-1, beta-2 antagonist), and 3) exercise plus metoprolol (a specific beta-1 antagonist). The basal potassium concentration was similar in all three studies and averaged 4.95 ± 0.12 mEq/liter. During Study 1 (exercise alone), plasma potassium rose by 0.26 ± 0.09 mEq/liter. During exercise with propranolol, plasma K concentration rose significantly higher (Δ plasma K = 0.44 ± 0.26 mEq/liter; P < 0.05 vs. exercise alone). In contrast, the rise in plasma K during exercise with metoprolol (Δ plasma K = 0.20 ± 0.08 mEq/liter) was similar to that observed with exercise alone. Differences in potassium homeostasis between metoprolol and propranolol could not be explained by differences in hemodynamic parameters, levels of potassium regulatory hormones, or acid base status. Thus, the higher rise in potassium concentration during exercise with propranolol could only be explained by adrenergic blockade at the beta-2 receptor site. These results support the concept that adrenergic control of extrarenal potassium homeostasis in dialysis patients is mediated at the beta-2 receptor. Since a deterioration in potassium homeostasis during exercise is observed with beta-2, but not beta-1 blockade, selective beta-1 adrenergic blocking agents may be safer in dialysis patients

Epinephrine and potassium homeostasis

Epinephrine and potassium homeostasis. The effect of epinephrine on potassium metabolism was examined in six subjects. Each subject participated in four studies as follows: (1) potassium chloride infusion (0.75 mEq/kg, i.v.) given over 2 hours, (2) epinephrine (0.05 µg/kg·min) plus potassium chloride, (3) propranolol (1.43 µg/kg·min) plus epinephrine plus potassium chloride, and (4) propranolol plus potassium chloride. The epinephrine infusion with potassium chloride led to a marked improvement in potassium tolerance, which was due to a greater than twofold increase in the extrarenal disposal of potassium (P < 0.001). The enhancing effect of epinephrine on extrarenal potassium uptake was completely reversed with the beta-blocking agent propranolol. When propranolol alone was infused with potassium chloride, a significant decrease in the extrarenal disposal of potassium was observed. When potassium chloride was infused alone, 47% of the administered potassium load was excreted in the urine. Epinephrine infusion with potassium chloride markedly inhibited the urinary excretion of potassium (UKV) to rates that were actually below the basal potassium excretion rate (P <0.001). Propranolol almost completely reversed this effect of epinephrine on UKV, and when propranolol was infused alone, an enhancement in UKV (P < 0.005) was observed. Insulin adds only a minor contribution to the enhancing effect of epinephrine on extrarenal potassium disposal and does not contribute at all to the inhibitory effect of epinephrine on renal potassium excretion. These results demonstrate that epinephrine ameliorates the rise in plasma potassium concentration following potassium chloride infusion. Because none of the infused potassium was excreted during the 4-hour study period, the improvement in potassium tolerance must result from an enhancement in extrarenal potassium disposal. The ability of propranolol to reverse both the extrarenal and renal effects indicates that the action of epinephrine is mediated via stimulation of the beta receptor.Epinéphrine et homéostasie du potassium. L'effet de l'épinéphrine sur le métabolisme du potassium a été étudié chez six sujets. Chaque sujet a participé à quatre études de la façon suivante: (1) perfusion de chlorure de potassium (0,75 mEq/kg, i.v.) administré en 2 heures, (2) épinéphrine (0,05 µg/kg·min) plus chlorure de potassium, (3) propranolol (1,43 µg/kg·min) plus épinéphrine plus chlorure de potassium, et (4) propranolol plus chlorure de potassium. La perfusion d'épinéphrine avec du chlorure de potassium détermine une augmentation importante de la tolérance au potassium, laquelle est due à une augmentation de plus du double de la disposition extra-rénale du potassium (P < 0,001). L'effet d'augmentation par l'épinéphrine de la captation extra-rénale du potassium a été complètement aboli par le bêta bloquant propranolol. Quand le propsranolol seul a été perfusé avec du chlorure de potassium, une diminution significative de la disposition extra-rénale de potassium a été observée. Quand le chlorure de potassium est perfusé seul, 47% de la charge administrée sont excrétés dans les urines. La perfusion d'épinéphrine avec le chlorure de potassium a abaissé de façon importante UKV à des débits inférieurs aux valeurs basales (P < 0,001). Le propranolol abolit presque complètement cet effet de l'épinéphrine sur UKV et quand le propranolol est perfusé seul une augmentation de UKV (P < 0,005) apparaît. L'insuline n'apporte qu'une faible contribution à l'effet d'augmentation par l'épinéphrine de la disposition extra-rénale du potassium et ne contribue pas du tout à l'effet inhibiteur de l'épinéphrine sur l'excrétion rénale de potassium. Ces résultats démontrent que l'épinéphrine minimise l'élévation de la concentration plasmatique de potassium consécutive à une perfusion de chlorure de potassium. Du fait que le potassium perfusé n'est pas excrété pendant les 4 heures de l'étude il est prouvé que l'amélioration de la tolérance au potassium est la conséquence d'une augmentation de sa disposition extra-rénale. La capacité qu'a le propranolol d'abolir à la fois l'effet rénal et l'effet extra-rénal indique que cette action de l'épinéphrine a pour médiateur la stimulation des récepteurs bêta

Creative destruction in science

Drawing on the concept of a gale of creative destruction in a capitalistic economy, we argue that initiatives to assess the robustness of findings in the organizational literature should aim to simultaneously test competing ideas operating in the same theoretical space. In other words, replication efforts should seek not just to support or question the original findings, but also to replace them with revised, stronger theories with greater explanatory power. Achieving this will typically require adding new measures, conditions, and subject populations to research designs, in order to carry out conceptual tests of multiple theories in addition to directly replicating the original findings. To illustrate the value of the creative destruction approach for theory pruning in organizational scholarship, we describe recent replication initiatives re-examining culture and work morality, working parents\u2019 reasoning about day care options, and gender discrimination in hiring decisions. Significance statement It is becoming increasingly clear that many, if not most, published research findings across scientific fields are not readily replicable when the same method is repeated. Although extremely valuable, failed replications risk leaving a theoretical void\u2014 reducing confidence the original theoretical prediction is true, but not replacing it with positive evidence in favor of an alternative theory. We introduce the creative destruction approach to replication, which combines theory pruning methods from the field of management with emerging best practices from the open science movement, with the aim of making replications as generative as possible. In effect, we advocate for a Replication 2.0 movement in which the goal shifts from checking on the reliability of past findings to actively engaging in competitive theory testing and theory building. Scientific transparency statement The materials, code, and data for this article are posted publicly on the Open Science Framework, with links provided in the article

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI &lt;18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For school&#x2;aged children and adolescents, we report thinness (BMI &lt;2 SD below the median of the WHO growth reference) and obesity (BMI &gt;2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit