Regulation of Apical NHE3 Trafficking by Ouabain-Induced Activation of Basolateral Na/K-ATPase Receptor Complex

The long-term effects of ouabain on transepithelial Na+ transport involve transcriptional downregulation of apical Na+/H+ exchanger isoform 3 (NHE3). The aim of this study was to determine whether ouabain could acutely regulate NHE3 via a posttranscriptional mechanism in LLC-PK1 cells. We observed that the basolateral, but not apical, application of ouabain for 1 h significantly reduced transepithelial Na+ transport. This effect was not due to changes in the integrity of tight junctions or increases in the intracellular Na+ concentration. Ouabain regulated the trafficking of NHE3 and subsequently inhibited its activity, a process independent of intracellular Na+ concentration. Ouabain-induced NHE3 trafficking was abolished by either cholesterol depletion or Src inhibition. Moreover, ouabain increased the intracellular Ca2+concentration. Pretreatment of cells with the intracellular Ca2+ chelator BAPTA-AM blocked ouabain-induced trafficking of NHE3. Also, blockade of Na+-K+-ATPase endocytosis by a phosphatidylinositol 3-kinase inhibitor was equally effective in attenuating ouabain-induced NHE3 trafficking. These data indicate that ouabain acutely stimulates NHE3 trafficking by activating the basolateral Na+-K+-ATPase signaling complex. Taken together with our previous observations, we propose that ouabain can simultaneously regulate basolateral Na+-K+-ATPase and apical NHE3, leading to inhibition of transepithelial Na+ transport. This mechanism may be relevant to proximal tubular Na+ handling during conditions associated with increases in circulating endogenous cardiotonic steroids

Elevated Plasma Total Cholesterol Level Is Associated with the Risk of Asymptomatic Intracranial Arterial Stenosis

Background: Intracranial arterial stenosis (ICAS) is one of the most common causes of stroke, and dyslipidemia was one of the most common risk factors related to ICAS. However, the correlation between the plasma total cholesterol level (PTC) and ICAS, especially asymptomatic ICAS (AICAS) is not clear. Materials and Methods 5,300 participants were enrolled in this study. The diagnosis of AICAS was made by transcranial Doppler ultrasonography. The participants were then divided into 5 essentially equal-sized groups based on their PTC levels. The multivariate logistic regression was used to analyze the correlation between the PTC level and the prevalence of AICAS. Results: 13.0% of the participants were diagnosed with AICAS. The prevalence of AICAS gradually increased with the increasing PTC level. After adjusted by the possible confounding factors, the Odds Ratios (OR) of the AICAS prevalence between the 1st quintile group and the other 4 groups were 1.13, 1.23, 1.63 and 1.75 with 95% confident intervals (CI) of 0.84–1.52, 0.91–1.66, 1.20–2.22 and 1.23–2.47, respectively. The further subgroup analysis revealed that the PTC level was stronger for males (OR 1.42 95%CI 1.23–1.64), regarding the prevalence of AICAS. Conclusions: In this large community-based study, the prevalence of AICAS is 13.0%, subjects with higher PTC levels showed a mild increase in the prevalence of AICAS. The PTC level is an independent risk factor of AICAS. Males seem to be significantly more vulnerable to the risk of AICAS

Patients with Parkinson\u27s Disease Experience Increased Perioperative Complications Following Cervical Decompression and Fusion: A Retrospective Review of the National Inpatient Sample

BACKGROUND: Despite improved medical management, incidence of spinal pathology remains high in patients with Parkinson\u27s disease (PD). Several studies have investigated lumbar spine surgery in this population, but data regarding costs and perioperative complications for patients undergoing cervical decompression/fusion on a nationwide scale is lacking. METHODS: Cases of cervical spinal decompression, fusion, or exploration in years 2008-2014 were collected via the Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS). Demographics, complications, outcome and total charges were compared in patients with and without PD (NPD). Confounding variables were identified for multivariate analysis. RESULTS: Data were available for 195,341 cervical spine cases, of which PD was prevalent in 779 cases (0.4%). Cases with PD experienced higher overall complication rates (12.5 vs. 7.6%; p\u3c 0.001). Multivariate analysis revealed longer lengths of stay for the PD cohort (mean = 1.21 days longer; p\u3c 0.001) and decreased routine discharge (OR = 0.308; p\u3c 0.001). There was no significant difference in mean total charges between PD and NPD ($-1,532; p= 0.337). Mortality rates did not significantly differ for either group. CONCLUSIONS: Although patients with PD experience higher complication rates and non-home discharges following cervical spine surgery compared to NPD patients, the overall clinical impact of these results may be minimal relative to surgery at other spinal levels in this population

Multivariate-adjusted odd ratios (OR) for AICAS between different PTC quintile groups, stratified by age, sex and selected risk factors.

<p>* P<0.05; ** P<0.001.</p><p>AICAS: asymptomatic intracranial artery stenosis; BMI: body mass index; PTC: plasma total cholesterol.</p><p>PTC levels: Q1≤4.23 mmol/l, Q2 4.24–4.72 mol/l, Q3 4.73–5.19 mmol/l, Q4 5.20–5.80 mmol/l and Q5≥5.81 mmol/l.</p><p>Multivariate-adjusted odd ratios (OR): adjusted for age, sex, hypertension, diabetes, smoking, family history of myocardial infarction and stroke, BMI, SBP, DBP, FBG, LDL-C, HDL-C, TG, anti-hypertension treatment and sex*PTC.</p><p># additionally adjusted for menopausal status.</p

The incidence of stenosis in different intracranial arteries.

<p>ACA: anterior cerebral artery; BA: basal artery; MCA: middle cerebral artery; PCA: posterior cerebral artery; SIPH: siphon carotid artery; VA: vetebral artery.</p

The prevalence of AICAS in each PTC quintile group.

<p>AICAS: asymptomatic intracranial artery stenosis; PTC: plasma total cholesterol.</p

Odd ratios (OR) for AICAS between different PTC quintile groups.

<p>* P<0.05;</p><p>** P<0.001.</p><p>95%CI: 95% confidence interval; AICAS: asymptomatic intracranial artery stenosis; MI: myocardial infarction; PTC: plasma total cholesterol.</p><p>PTC levels: Q1≤4.23 mmol/l, Q2 4.24–4.72 mol/l, Q3 4.73–5.19 mmol/l, Q4 5.20–5.80 mmol/l and Q5≥5.81 mmol/l.</p><p>Model 1: adjusted for age, sex;</p><p>Model 2: adjusted for age, sex, hypertension, diabetes, smoking, family history of myocardial infarction and stroke, BMI, SBP, DBP, FBG, LDL-C, HDL-C, TG, anti-hypertension treatment and sex*PTC.</p