scholarly journals The Off-Target Effects, Electrolyte and Mineral Disorders of SGLT2i

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2757 ◽  
Author(s):  
Giuseppe Cianciolo ◽  
Antonio De Pascalis ◽  
Lorenzo Gasperoni ◽  
Francesco Tondolo ◽  
Fulvia Zappulo ◽  
...  
Keyword(s):  
Experimental Studies ◽  
Sodium Balance ◽  
Calcium Excretion ◽  
Sodium Transporters ◽  
New Class ◽  
Sodium Glucose Cotransporter ◽  
Natriuretic Effect ◽  
Sodium Handling ◽  
Target Effects

The sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a relatively new class of antidiabetic drugs that, in addition to emerging as an effective hypoglycemic treatment, have been shown to improve, in several trials, both renal and cardiovascular outcomes. In consideration of the renal site of action and the associated osmotic diuresis, a negative sodium balance has been postulated during SGLT2i administration. Although it is presumable that sodium and water depletion may contribute to some positive actions of SGLT2i, evidence is far from being conclusive and the real physiologic effects of SGLT2i on sodium remain largely unknown. Indeed, no study has yet investigated how SGLT2i change sodium balance in the long term and especially the pathways through which the natriuretic effect is expressed. Furthermore, recently, several experimental studies have identified different pathways, not directly linked to tubular sodium handling, which could contribute to the renal and cardiovascular benefits associated with SGLT2i. These compounds may also modulate urinary chloride, potassium, magnesium, phosphate, and calcium excretion. Some changes in electrolyte homeostasis are transient, whereas others may persist, suggesting that the administration of SGLT2i may affect mineral and electrolyte balances in exposed subjects. This paper will review the evidence of SGLT2i action on sodium transporters, their off-target effects and their potential role on kidney protection as well as their influence on electrolytes and mineral homeostasis.

scholarly journals Sodium glucose cotransporter 2 inhibitors: mechanisms of action in heart failure

2020 ◽  
Author(s):  
Mieczysław Dutka ◽  
Rafał Bobiński ◽  
Izabela Ulman-Włodarz ◽  
Maciej Hajduga ◽  
Jan Bujok ◽  
...  
Keyword(s):  
Heart Failure ◽  
Glycaemic Control ◽  
Experimental Studies ◽  
Mechanisms Of Action ◽  
New Class ◽  
Current State ◽  
Sodium Glucose Cotransporter ◽  
Patients With Diabetes ◽  
Clinical Benefits ◽  
Treatment Of Diabetes

Abstract Diabetes is a key independent risk factor in the development of heart failure (HF) and a strong, adverse prognostic factor in HF patients. HF remains the primary cause of hospitalisation for diabetics and, as previous studies have shown, when HF occurs in these patients, intensive glycaemic control does not directly improve the prognosis. Recent clinical studies assessing a new class of antidiabetic drugs, sodium-glucose cotransporter 2 inhibitors (SGLT2is) showed some unexpected beneficial results. Patients treated with SGLT2is had a significant decrease in both cardiovascular (CV) and all-cause mortality and less hospitalisations due to HF compared to those given a placebo. These significant clinical benefits occurred quickly after the drugs were administered and were not solely due to improved glycaemic control. These groundbreaking clinical trials’ results have already changed clinical practice in the management of patients with diabetes at high CV risk. These trials have triggered numerous experimental studies aimed at explaining the mechanisms of action of this unique group of drugs. This article presents the current state of knowledge about the mechanisms of action of SGLT2is developed for the treatment of diabetes and which, thanks to their cardioprotective effects, may, in the future, become a treatment for patients with HF.

scholarly journals Sodium Handling and Interaction in Numerous Organs

2020 ◽  
Vol 33 (8) ◽  
pp. 687-694 ◽  
Author(s):  
Shintaro Minegishi ◽  
Friedrich C Luft ◽  
Jens Titze ◽  
Kento Kitada
Keyword(s):  
Salt Content ◽  
The Body ◽  
Sodium Balance ◽  
Plasma Sodium ◽  
Great Effort ◽  
Salt Balance ◽  
Long Term Study ◽  
Salt Excretion ◽  
Sodium Handling

Abstract Salt (NaCl) is a prerequisite for life. Excessive intake of salt, however, is said to increase disease risk, including hypertension, arteriosclerosis, heart failure, renal disease, stroke, and cancer. Therefore, considerable research has been expended on the mechanism of sodium handling based on the current concepts of sodium balance. The studies have necessarily relied on relatively short-term experiments and focused on extremes of salt intake in humans. Ultra-long-term salt balance has received far less attention. We performed long-term salt balance studies at intakes of 6, 9, and 12 g/day and found that although the kidney remains the long-term excretory gate, tissue and plasma sodium concentrations are not necessarily the same and that urinary salt excretion does not necessarily reflect total-body salt content. We found that to excrete salt, the body makes a great effort to conserve water, resulting in a natriuretic-ureotelic principle of salt excretion. Of note, renal sodium handling is characterized by osmolyte excretion with anti-parallel water reabsorption, a state-of-affairs that is achieved through the interaction of multiple organs. In this review, we discuss novel sodium and water balance concepts in reference to our ultra-long-term study. An important key to understanding body sodium metabolism is to focus on water conservation, a biological principle to protect from dehydration, since excess dietary salt excretion into the urine predisposes to renal water loss because of natriuresis. We believe that our research direction is relevant not only to salt balance but also to cardiovascular regulatory mechanisms.

Ultra long-term sodium balance studies during the Mars500 campaign

2012 ◽  
Vol 37 (03) ◽  
Author(s):  
N Rakova ◽  
K Jüttner ◽  
M Rauh ◽  
A Dahlmann ◽  
U Goller ◽  
...  
Keyword(s):  
Sodium Balance

Masonry: the brittle or plastic material?

2019 ◽  
pp. 22-28
Keyword(s):  
Plastic Material ◽  
Experimental Studies ◽  
Point Of View ◽  
Plastic Properties ◽  
Plastic Deformations ◽  
Base Materials ◽  
Stress States ◽  
Creep Deformations ◽  
Structural Point

The results of experimental studies of masonry on the action of dynamic and static (short-term and long-term) loads are presented. The possibility of plastic deformations in the masonry is analyzed for different types of force effects. The falsity of the proposed approach to the estimation of the coefficient of plasticity of masonry, taking into account the ratio of elastic and total deformations of the masonry is noted. The study of the works of Soviet scientists revealed that the masonry under the action of seismic loads refers to brittle materials in the complete absence of plastic properties in it in the process of instantaneous application of forces. For the cases of uniaxial and plane stress states of the masonry, data on the coefficient of plasticity obtained from the experiment are presented. On the basis of experimental studies the influence of the strength of the so-called base materials (brick, mortar) on the bearing capacity of the masonry, regardless of the nature of the application of forces and the type of its stress state, is noted. The analysis of works of prof. S. V. Polyakov makes it possible to draw a conclusion that at the long application of the load, characteristic for the masonry are not plastic deformations, but creep deformations. It is shown that the proposals of some authors on the need to reduce the level of adhesion of the mortar to the brick for the masonry erected in earthquake-prone regions in order to improve its plastic properties are erroneous both from the structural point of view and from the point of view of ensuring the seismic resistance of structures. It is noted that the proposal to assess the plasticity of the masonry of ceramic brick walls and large-format ceramic stone with a voidness of more than 20% is incorrect, and does not meet the work of the masonry of hollow material. On the basis of the analysis of a large number of research works it is concluded about the fragile work of masonry.

Improvement Of Curvilinear Diagrams Of Concrete Deformation

2019 ◽  
pp. 99-104
Keyword(s):  
Reinforced Concrete ◽  
Peak Load ◽  
Experimental Studies ◽  
Concrete Structures ◽  
Deformation Model ◽  
Reinforced Concrete Structures ◽  
Significant Difference ◽  
Deformation Diagrams

Problems when calculating reinforced concrete structures based on the concrete deformation under compression diagram, which is presented both in Russian and foreign regulatory documents on the design of concrete and reinforced concrete structures are considered. The correctness of their compliance for all classes of concrete remains very approximate, especially a significant difference occurs when using Euronorm due to the different shape and sizes of the samples. At present, there are no methodical recommendations for determining the ultimate relative deformations of concrete under axial compression and the construction of curvilinear deformation diagrams, which leads to limited experimental data and, as a result, does not make it possible to enter more detailed ultimate strain values into domestic standards. The results of experimental studies to determine the ultimate relative deformations of concrete under compression for different classes of concrete, which allowed to make analytical dependences for the evaluation of the ultimate relative deformations and description of curvilinear deformation diagrams, are presented. The article discusses various options for using the deformation model to assess the stress-strain state of the structure, it is concluded that it is necessary to use not only the finite values of the ultimate deformations, but also their intermediate values. This requires reliable diagrams "s–e” for all classes of concrete. The difficulties of measuring deformations in concrete subjected to peak load, corresponding to the prismatic strength, as well as main cracks that appeared under conditions of long-term step loading are highlighted. Variants of more accurate measurements are proposed. Development and implementation of the new standard GOST "Concretes. Methods for determination of complete diagrams" on the basis of the developed method for obtaining complete diagrams of concrete deformation under compression for the evaluation of ultimate deformability of concrete under compression are necessary.

scholarly journals Understanding sex differences in long-term blood pressure regulation: insights from experimental studies and computational modeling

2019 ◽  
Vol 316 (5) ◽  
pp. H1113-H1123 ◽  
Author(s):  
Sameed Ahmed ◽  
Rui Hu ◽  
Jessica Leete ◽  
Anita T. Layton
Keyword(s):  
Blood Pressure ◽  
Sex Differences ◽  
Computational Models ◽  
Experimental Studies ◽  
Pressure Control ◽  
Blood Pressure Regulation ◽  
Pressure Regulation ◽  
Physiological Processes ◽  
Key Players

Sex differences in blood pressure and the prevalence of hypertension are found in humans and animal models. Moreover, there has been a recent explosion of data concerning sex differences in nitric oxide, the renin-angiotensin-aldosterone system, inflammation, and kidney function. These data have the potential to reveal the mechanisms underlying male-female differences in blood pressure control. To elucidate the interactions among the multitude of physiological processes involved, one may apply computational models. In this review, we describe published computational models that represent key players in blood pressure regulation, and highlight sex-specific models and their findings.

scholarly journals Implementation Intentions to Reduce Smoking: A Systematic Review of the Literature

2020 ◽  
Author(s):  
Charlotte J Hagerman ◽  
Rebecca K Hoffman ◽  
Sruthi Vaylay ◽  
Tonya Dodge
Keyword(s):  
Systematic Review ◽  
Implementation Intentions ◽  
Experimental Studies ◽  
Implementation Intention ◽  
Promising Tool ◽  
Current Systematic Review ◽  
Long Term Follow Up ◽  
Positive Effect

Abstract Implementation intentions are a goal-setting technique in which an individual commits to perform a particular behavior when a specific context arises. Recently, researchers have begun studying how implementation intention (II) interventions can facilitate antismoking efforts. The current systematic review synthesized results of experimental studies that tested the effect of an II intervention on smoking cognitions and behavior. Of 29 reviewed articles, 11 studies met inclusion criteria. Nine studies (81.8%) tested an II intervention as a cessation tool for current smokers, whereas two tested II interventions as a tool to prevent smoking among predominantly nonsmoking adolescents. A majority of the studies (66.7%) testing II interventions as a cessation tool reported a positive effect on cessation at long-term follow-up. Of the two studies testing II interventions as a tool for prevention, one study found a positive effect on long-term follow-up. Methodology varied between the studies, highlighting the discrepancies between what researchers consider “implementation intentions” to be. II interventions are a promising tool for antismoking efforts, but more research is necessary to determine the best methodology and the populations for whom this intervention will be most effective. Implications Brief, free, and easily scalable, II interventions to prevent smoking are highly attractive for antismoking efforts. This review outlines the circumstances under which II interventions have demonstrated effectiveness in helping people resist smoking cigarettes. We illuminate gaps in the existing literature, limitations, methodological discrepancies between studies, and areas for future study.

Manipulating Environmental Commitment: A Replication and Extension

2021 ◽  
pp. 003329412110126
Author(s):  
Eric D. Wesselmann ◽  
Shane W. Boyd ◽  
Jordan A. Arellanes ◽  
Alexander Driskell ◽  
Matthew S. Hesson-McInnis
Keyword(s):  
Natural Environment ◽  
Behavioral Intentions ◽  
Subjective Experience ◽  
Experimental Studies ◽  
Environmental Commitment

Environmental commitment, the subjective experience of dependence on the natural environment, is marked by a long-term orientation and psychological attachment towards the natural environment. The current research replicates and extends previous research on temporarily increasing environmental commitment ( Davis et al., 2009 ). We employed Davis et al.’s manipulation in two experimental studies (one laboratory, one online): we asked participants to spend time writing either about ways in which they are interdependent with the natural environment (high commitment manipulation) or unconnected with the environment (low commitment manipulation). In both studies we replicated the key finding that reflecting on one’s interdependence with the environment increases commitment. We extended the previous research by finding evidence that this commitment effect was mediated by satisfaction with one’s relationship to the environment. We did not replicate the original findings that the interdependence manipulation influences environmental behavioral intentions.

scholarly journals Leopard Density Estimation within an Enclosed Reserve, Namibia Using Spatially Explicit Capture-Recapture Models

Animals ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 724
Author(s):  
Noack ◽  
Heyns ◽  
Rodenwoldt ◽  
Edwards
Keyword(s):  
Management Strategies ◽  
Camera Traps ◽  
Spatially Explicit ◽  
Conservation Areas ◽  
Term Survival ◽  
New Class ◽  
Capture Recapture ◽  
Wildlife Populations ◽  
Effective Conservation

The establishment of enclosed conservation areas are claimed to be the driving force for the long-term survival of wildlife populations. Whilst fencing provides an important tool in conservation, it simultaneously represents a controversial matter as it stops natural migration processes, which could ultimately lead to inbreeding, a decline in genetic diversity and local extinction if not managed correctly. Thus, wildlife residing in enclosed reserves requires effective conservation and management strategies, which are strongly reliant on robust population estimates. Here, we used camera traps combined with the relatively new class of spatially explicit capture-recaptured models (SECR) to produce the first reliable leopard population estimate for an enclosed reserve in Namibia. Leopard density was estimated at 14.51 leopards/100 km2, the highest recorded density in Namibia to date. A combination of high prey abundance, the absence of human persecution and a lack of top-down control are believed to be the main drivers of the recorded high leopard population. Our results add to the growing body of literature which suggests enclosed reserves have the potential to harbour high densities and highlight the importance of such reserves for the survival of threatened species in the future.

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