Browsing by Subject "Sodium"
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Item Acute Effect of High vs Low Dialysate Sodium on Endothelial Cell Function During Hemodialysis(2013-01-22) D'Silva, Kristin; Molina, Christopher; van Buren, Peter; Kim, Catherine; Inrig, JulaBACKGROUND: Intradialytic hypertension (HTN), a rise in blood pressure that occurs during hemodialysis (HD) treatments in up to 15% of patients, is associated with higher morbidity and mortality. The cause of intradialytic HTN is unknown but may be due to endothelial cell (EC) dysfunction. In vitro exposure of ECs to high sodium (Na+) concentration promotes EC stiffness and imbalances in vasoconstrictors (endothelin-1 [ET-1]) and vasodilators (nitric oxide [NO]). We hypothesized that, among patients with intradialytic HTN, exposure to high dialysate Na+ would lead to a decrease in NO and increase in ET-1 during HD. METHODS: We performed a 3-week, 2-arm, randomized crossover study among 16 HD patients with intradialytic HTN and compared the effects of high dialysate-to-serum Na+ gradients (5 mEq/L above participants' baseline Na+) vs low dialysate-to-serum Na+ gradients (5 mEq/L below baseline Na+ with lower limit of 134 mEq/L) on intradialytic changes in nitrite and ET-1. Differences between treatments were compared with repeated measures mixed linear regression and included randomization arm (high - low Na+ vs low - high Na+), treatment effect (high vs low Na+), subject, time and session. RESULTS: Study participants (N=16) had an average age of 58.8 years, 38% were black, 56% were Hispanic, and 94% were male. Intradialytic changes in NO and ET-1 with high and low dialysate-to-plasma Na+ gradients are shown in Figure 1. In the primary comparison of high vs low dialysate-to-serum Na+ gradient, there were no significant differences in intradialytic levels of NO or ET-1 (Table 1). However, when compared by randomization arm, participants who received the low dialysate-to-serum Na+ gradient followed by high compared to those who received the high dialysate-to-serum Na+ gradient followed by low had a significant decrease in ET-1 (parameter estimate -0.49 pg/mL, p=0.04) and significant increase in nitrite during hemodialysis (parameter estimate +0.16 nM, p=0.02) (Table 1). CONCLUSIONS: Patients who received the low dialysate-to-serum Na+ gradient before the high dialysate-to-serum Na+ gradient had higher levels of nitrite and lower levels of ET-1 throughout the three week study period compared to patients who received the high dialysate-to-serum Na+ gradient before the low dialysate-to-serum Na+ gradient. This suggests that the dialysate Na+ concentration may have longer-term effects on endothelial cell function.Item Atrial natriuretic factor(1985-08-22) Henrich, William L.Item New insights into the pathogensis of hypertension: the role of sodium and calcium(1982-11-18) Kaplan, Norman M.Item Newer approaches to the therapy of hypertension(1986-03-13) Kaplan, Norman M.Item [News](1979-09) Williams, AnnItem Pathogenesis of edema(1966-12-01) Rector, Floyd C.Item [Southwestern News](2005-07-06) Siegfried, AmandaItem Structure and Function of the Alpha3Beta4 Nicotinic Acetylcholine Receptor(2020-12-01T06:00:00.000Z) Gharpure, Anant Vishwanath; Jiang, Youxing; Zhang, Xuewu; Bai, Xiaochen; Hibbs, Ryan E.Nicotinic acetylcholine receptors are pentameric ligand-gated ion channels that are essential for the proper function of the central and peripheral nervous systems. The α3β4 subtype is highly expressed in the autonomic ganglia, where it contributes to signal transduction from the central nervous system to the periphery. Moreover, α3β4 receptors are found in key brain regions that modulate reward circuits and have therefore been identified as potential targets for anti-addiction therapeutics. Given the physiological importance of this protein, I sought to understand the molecular mechanisms underlying ligand recognition, channel gating, and ion permeation in the α3β4 nicotinic acetylcholine receptor. Paramount to this goal was the pursuit of a high-resolution structure of the α3β4 subtype. I initially attempted to determine a crystal structure of this receptor before taking advantage of recent technological advances in cryo-electron microscopy. Using this method, I solved the first structure of the α3β4 nicotinic receptor, which was also the first high-resolution structure of any nicotinic acetylcholine receptor in a lipidic environment. By obtaining structural information of the protein bound to a non-selective nicotinic agonist as well as an α3β4-selective ligand, I was able to draw conclusions regarding ligand-selectivity in the nicotinic receptor family. Furthermore, these structures provided a detailed view of the ordered regions of the intracellular domain for the first time, giving insight into the full ion permeation pathway of these channels. This work also provided a blueprint to examine other outstanding questions in the field. Specifically, I used structural and functional approaches to begin to understand the consequences of accessory subunit incorporation, the role of multivalent cations in the desensitization of nicotinic receptors, and the role of the intracellular domain in ion selectivity and rectification.Item Urine Sodium Concentration as a Marker of Poor Growth in Children with Intestinal Failure(2017-01-17) Casson, Cameron; Piper, Hannah; Pace, JesseBACKGROUND: Children who have had a significant small bowel resection often have difficulty growing adequately due to fluid and electrolyte losses in their stool. Specifically, growth is impaired when total body sodium depletion occurs. Urinary sodium concentration (UNa) is a more sensitive marker than serum sodium (less than or equal to 30 mmol/L considered low), and is used to monitor total body sodium status. The objective of this study was to determine the frequency of low UNa in children after significant bowel resection, and determine if it is associated with poor growth. METHODS: After IRB approval (Protocol #032016-015), a retrospective chart review of children (<19 years) who underwent small bowel resection (requiring parenteral nutrition for > 6 weeks post-operatively) cared for at Children's Health from 2010 to 2016 was performed. Patient characteristics, reason for small bowel resection, intestinal anatomy, nutritional intake, anthropometric measurements, and urine and serum electrolytes were collected. Z-scores were calculated from WHO and CDC standard growth charts. Anthropometric values were compared between children with a UNa less than or equal to 30 mmol/L and > 30 mmol/L. Statistical analysis was completed using Mann-Whitney and Pearson's correlation coefficient, providing both 95% confidence intervals and p-values. Analysis was performed with SAS 9.4 (Cary, NC). RESULTS: Thirty-eight children with significant bowel resection were included in the study. Patients had a median small bowel length of 50 cm (5-315 cm) and median % expected small bowel remaining of 27% (2-91%). The median UNa was 44 mmol/L, and 10 patients (26%) had a UNa less than or equal to, to 30 mmol/L. Only 1 patient demonstrated hyponatremia (serum Na = 130 meq/L). There was a positive correlation between UNa and both sodium intake (0.32, 95% CI [0.01, 0.57], p=.04), and body mass index (0.35, 95% CI [0.05, 0.60], p=.03), but no significant correlation with small bowel length. Children with UNa less than or equal to 30mmol/L had significantly lower Z-scores for weight (median -2.5 vs. -0.44, p=.0252) compared to those with UNa > 30mmol/L. CONCLUSION: Children with malabsorption after significant small bowel resection are at increased risk for sodium depletion and impaired growth. Patients with UNa less than or equal to 30 mmol/L should receive additional sodium supplementation to maximize growth.