Empagliflozin Changes Urine Supersaturation by Decreasing pH and Increasing Citrate.
Ontology highlight
ABSTRACT:
SUBMITTER: Harmacek D
PROVIDER: S-EPMC9161803 | biostudies-literature | 2022 Jun
REPOSITORIES: biostudies-literature
Publications
Empagliflozin Changes Urine Supersaturation by Decreasing pH and Increasing Citrate.
Harmacek Dusan D Pruijm Menno M Burnier Michel M Muller Marie-Eve ME Ghajarzadeh-Wurzner Arlène A Bonny Olivier O Zanchi Anne A
Journal of the American Society of Nephrology : JASN 20220406 6
<b>Clinical Trial registry name and registration number:</b> Empagliflozin and Renal Oxygenation in Healthy Volunteers (EMPA-REIN), NCT03093103. ...[more]
Similar Datasets
Project description: Not available
| S-EPMC10476682 | biostudies-literature
Project description:Urolithiasis is highly prevalent in dogs and cats, with struvite and calcium oxalate being most commonly diagnosed. Some commercial diets aimed at reducing the risk of urolithiasis are based on inclusion of sodium chloride (NaCl) in an attempt to dilute the urine and the risk of crystallization, but more information on the effect of differing levels of sodium inclusion is needed. The objective of this study was to compare the short-term effect of four diets differing only in NaCl content (base diet with 0.3% sodium and diets with added NaCl to achieve 0.7, 1.0 and 1.3% sodium as fed) on urinary ion concentrations and relative supersaturation (RSS) of struvite and calcium oxalate in dogs and cats. In both species, there was a significant increase in water intake and urine volume as dietary NaCl increased. Urine sodium concentration increased with increasing dietary NaCl. The highest sodium diet increased urinary calcium excretion in dogs only, while decreasing urinary calcium concentration. Calcium oxalate RSS and struvite RSS both significantly decreased, with the lowest RSS values reported on the highest sodium diet in both dogs and cats (p < .001). These results suggest that an increase in dietary NaCl decreases RSS values in both dogs and cats. Despite an increase in urinary calcium excretion in dogs, urinary calcium concentration and calcium oxalate RSS were lower on high sodium diets due to urine dilution. Long-term studies are needed to confirm the relationship between RSS and stone occurrence and recurrence.
| S-EPMC7540452 | biostudies-literature
Project description:PurposeThe relative supersaturation of calcium oxalate, calcium phosphate and uric acid is used clinically in kidney stone prevention. The magnitude of the association between relative supersaturation and stone risk requires further quantification.Materials and methodsWe performed a cross-sectional study using 24-hour urine collections from the NHS (Nurses' Health Study) I and II, and HPFS (Health Professionals Follow-up Study) cohorts to quantify the association between the relative supersaturation of calcium oxalate, calcium phosphate and uric acid, and the likelihood of stone formation.ResultsThe OR of being a stone former was 5.85 (95% CI 3.40-10.04) in NHS I, 6.38 (95% CI 3.72-11.0) in NHS II and 6.95 (95% CI 3.56-13.6) in HPFS for the highest category of calcium oxalate relative supersaturation compared with less than 1.0. The OR of being a stone former was 1.86 (95% CI 0.94-3.71) in NHS I, 4.37 (95% CI 2.68-7.10) in NHS II and 3.59 (95% CI 2.04-6.31) in HPFS for the highest category of calcium phosphate relative supersaturation compared with less than 1.0. For uric acid relative supersaturation the OR of being a stone former was 4.30 (95% CI 2.34-7.90) in NHS I and 2.74 (95% CI 1.71-4.40) in NHS II for the highest relative supersaturation category compared with less than 1.0. In HPFS the uric acid relative supersaturation was not significantly associated with the likelihood of stone formation.ConclusionsThe likelihood of being a stone former increases with higher relative supersaturation of calcium oxalate and calcium phosphate in men and women, and with higher relative supersaturation of uric acid in women.
| S-EPMC5911189 | biostudies-literature
Project description:ObjectiveThe primary purpose was to determine how trust changes over time when automation reliability increases or decreases. A secondary purpose was to determine how task-specific self-confidence is associated with trust and reliability level.BackgroundBoth overtrust and undertrust can be detrimental to system performance; therefore, the temporal dynamics of trust with changing reliability level need to be explored.MethodTwo experiments used a dominant-color identification task, where automation provided a recommendation to users, with the reliability of the recommendation changing over 300 trials. In Experiment 1, two groups of participants interacted with the system: one group started with a 50% reliable system which increased to 100%, while the other used a system that decreased from 100% to 50%. Experiment 2 included a group where automation reliability increased from 70% to 100%.ResultsTrust was initially high in the decreasing group and then declined as reliability level decreased; however, trust also declined in the 50% increasing reliability group. Furthermore, when user self-confidence increased, automation reliability had a greater influence on trust. In Experiment 2, the 70% increasing reliability group showed increased trust in the system.ConclusionTrust does not always track the reliability of automated systems; in particular, it is difficult for trust to recover once the user has interacted with a low reliability system.ApplicationsThis study provides initial evidence into the dynamics of trust for automation that gets better over time suggesting that users should only start interacting with automation when it is sufficiently reliable.
| S-EPMC11487872 | biostudies-literature
Project description:Creating supersaturating drug delivery systems to overcome the poor aqueous solubility of active ingredients became a frequent choice for formulation scientists. Supersaturation as a solution phenomenon is, however, still challenging to understand, and therefore many recent publications focus on this topic. This work aimed to investigate and better understand the pH dependence of supersaturation of telmisartan (TEL) at a molecular level and find a connection between the physicochemical properties of the active pharmaceutical ingredient (API) and the ability to form supersaturated solutions of the API. Therefore, the main focus of the work was the pH-dependent thermodynamic and kinetic solubility of the model API, TEL. Based on kinetic solubility results, TEL was observed to form a supersaturated solution only in the pH range 3-8. The experimental thermodynamic solubility-pH profile shows a slight deviation from the theoretical Henderson-Hasselbalch curve, which indicates the presence of zwitterionic aggregates in the solution. Based on pKa values and the refined solubility constants and distribution of macrospecies, the pH range where high supersaturation-capacity is observed is the same where the zwitterionic form of TEL is present. The existence of zwitterionic aggregation was confirmed experimentally in the pH range of 3 to 8 by mass spectrometry.
| S-EPMC9412861 | biostudies-literature
Project description:Introduction Relative supersaturation (RSS) values for urine crystals are a measure of the risk of urinary stone formation and have been shown to be lowered in foods shown to aid in the management of urolithiasis. In order to calculate RSS in pets, computer programs have been developed to calculate RSS and aid in the understanding of stone formation in veterinary medicine. However, some older programs have not been updated for use in animals, and the specific coefficients used are not publically available. One of the first RSS programs was developed in BASIC computer language and published in 1985 which was called EQUIL2. The EQUIL2 program was updated to a compiled version compatible with a PC platform. However, the formulas could not be read or altered. Methods This study evaluates a new program with known coefficients to the original EQUIL2 program. The RSS values of the two programs were compared through a t-test, calculating the r2 from correlation analysis, Lin’s concordance correlation coefficient, and by a Bland–Altman analysis of outputs from the two programs using urine samples from healthy dogs and cats. Results and Discussion Our results show that for both magnesium ammonium phosphate (struvite) and calcium oxalate, the RSS values of the original program could be calculated from the new programs RSS values. Although the actual RSS values were different (as might be expected through the use of the updated coefficients and different thermodynamic stability constants in the calculations) the results were highly correlated, finding elevations and reductions in RSS proportionally in the same urine samples. The current work creates a foundation for using the modernized program to calculate RSS and provides a shared method for understanding the risk of struvite and calcium oxalate stone formation.
| S-EPMC10274322 | biostudies-literature
Project description:Plankton phototrophy consumes CO2, increasing seawater pH, while heterotrophy does the converse. Elevation of pH (>8.5) during coastal blooms becomes increasingly deleterious for plankton. Mixoplankton, which can be important bloom-formers, engage in both photoautotrophy and phagoheterotrophy; in theory, this activity could create a relatively stable pH environment for plankton growth. Using a systems biology modelling approach, we explored whether different mixoplankton functional groups could modulate the environmental pH compared to the extreme activities of phototrophic phytoplankton and heterotrophic zooplankton. Activities by most mixoplankton groups do not stabilize seawater pH. Through access to additional nutrient streams from internal recycling with phagotrophy, mixoplankton phototrophy is enhanced, elevating pH; this is especially so for constitutive and plastidic specialist non-constitutive mixoplankton. Mixoplankton blooms can exceed the size of phytoplankton blooms; the synergisms of mixoplankton physiology, accessing nutrition via phagotrophy as well as from inorganic sources, enhance or augment primary production rather than depressing it. Ocean acidification will thus enable larger coastal mixoplankton blooms to form before basification becomes detrimental. The dynamics of such bloom developments will depend on whether the mixoplankton are consuming heterotrophs and/or phototrophs and how the plankton community succession evolves.
| S-EPMC10361812 | biostudies-literature
Project description:In Lactococcus lactis subsp. lactis biovar diacetylactis, citrate transport is facilitated by the plasmid-encoded citrate permease (CitP). In this work, we analysed regulation of citrate utilization by pH, nutrient limitation and the presence of citrate at four different levels: (i) plasmid copy number, (ii) citP transcription, (iii) citP mRNA processing and (iv) citrate utilization capacity. Citrate was supplied as cosubstrate together with lactose. The citP gene is known to be induced in cells grown at low pH. However, we demonstrated that transcription of citP was even higher in the presence of citrate (3.8-fold compared with 2.0-fold). The effect of citrate has been overlooked by other researchers because they determined the effect of citrate using M17 medium, which already contains 0.80 ± 0.07 mM citrate. The plasmid copy number increased in cells grown under amino acid limitation (1.6-fold) and/or at low pH (1.4-fold). No significant differences in citP mRNA processing were found. Citrate utilization rates increased from approximately 1 to 65 μmol min-1 gDW-1 from lowest to highest citP expression. Acetoin formation increased during growth in an acidic environment due to induction of the acetoin pathway. Quantification of the relative contributions allowed us to construct a model for regulation of citrate utilization in L. lactis biovar diacetylactis. This knowledge will help to select conditions to improve flavour formation from citrate.
| S-EPMC5812246 | biostudies-literature
Project description:Two starch to protein ratios (high starch [HS], 25% starch and 36% protein; high protein [HP], 15% starch and 53% protein on DM basis) and two moisture contents (5%, dry kibbles; 80%, wet food) were compared in a 2 x 2 factorial arrangement totaling 4 diets. Each diet was evaluated in 9 cats, with 8 d of total collection of urine and feces. Results were subjected to an analysis of variance of the effects of starch to protein ratio, moisture content and their interactions (P<0.05). Urine density was lower and volume was higher in cats fed wet foods (P<0.01). Calcium (Ca) urine concentration was higher for dry and HP diets (P<0.05). The oxalate urine concentration was 60% higher for cats fed both HS formulations (dry and wet; P<0.05). The relative supersaturation (RSS) of urine for calcium oxalate was higher for dry foods and HS formulations (P<0.01), and for struvite, it was lower for both wet foods, and among the dry diets, it was lower for the HS than for the HP formulation (P<0.01). Foods with a high protein-to-starch ratio reduced urine oxalate and RSS for calcium oxalate in wet and dry diets, and wet foods reduced RSS for calcium oxalate and struvite.
| S-EPMC11654968 | biostudies-literature
Project description:The molecular chaperone Hsp90 depends upon large conformational rearrangements for its function. One driving force for these rearrangements is the intrinsic ATPase activity of Hsp90, as seen with other chaperones. However, unlike other chaperones, structural and kinetic studies have shown that the ATPase cycle of Hsp90 is not conformationally deterministic. That is, rather than dictating the conformational state, ATP binding and hydrolysis shift the equilibrium between a preexisting set of conformational states in an organism-dependent manner. While many conformations of Hsp90 have been described, little is known about how they relate to chaperone function. In this study, we show that the conformational equilibrium of the bacterial Hsp90, HtpG, can be shifted with pH. Using small-angle X-ray scattering, we identify a two-state pH-dependent conformational equilibrium for apo HtpG. Our structural modeling reveals that this equilibrium is observed between the previously observed extended state and a second state that is strikingly similar to the recently solved Grp94 crystal structure. In the presence of nonhydrolyzable 5'-adenylyl-beta,gamma-imidodiphosphate, a third state, which is identical with the solved AMPPNP-bound structure from yeast Hsp90, is populated. Electron microscopy confirmed the observed conformational equilibria. We also identify key histidine residues that control this pH-dependent equilibrium; using mutagenesis, we successfully modulate the conformational equilibrium at neutral pH. Using these mutations, we show that the Grp94-like state provides stronger aggregation protection compared to the extended apo conformation in the context of a citrate synthase aggregation assay. These studies provide a more detailed view of HtpG's conformational dynamics and provide the first linkage between a specific conformation and chaperone function.
| S-EPMC2735500 | biostudies-literature