NH4+ secretion in inner medullary collecting duct in potassium deprivation: role of colonic H+-K+-ATPase

NH4+ secretion in inner medullary collecting duct in potassium deprivation: Role of colonic H+-K+-ATPase. BACKGROUND: In K+ deprivation (KD), gastric (g) H+-K+-ATPase (HKA) is suppressed, whereas colonic (c) HKA is induced in the terminal inner medullary collecting duct (IMCD). We hypothesized that in KD, cHKA is induced and can mediate the secretion of NH4+. METHODS: Rats were sacrificed after 2, 3, 6, or 14 days on regular (NML) or K+-free (KD) diet. mRNA expression of HKA isoforms in terminal inner medulla was examined and correlated with NH4+ secretion in perfused IMCD in vitro. RESULTS: Urinary NH4+ excretion increased after K+-free diet for six days. In terminal inner medulla, cHKA expression was strongly induced, whereas gHKA expression was decreased. NH4+ secretion increased by 62% in KD (JtNH4+ 0.57 vs. 0.92 pmol/min/mm tubule length, P < 0.001). Ouabain (1 mM) in perfusate inhibited NH4+ secretion in KD by 45% (P < 0.002) but not in NML. At luminal pH 7.7, which inhibits NH3 diffusion, NH4+ secretion in IMCD was 140% higher in KD (0.36 vs. 0.15, P < 0.03) and was sensitive to ouabain. ROMK-1 mRNA expression was induced in parallel with cHKA in inner medulla. CONCLUSIONS: These data suggest that in KD, cHKA replaces gHKA and mediates enhanced secretion of NH4+ (and H+) into the lumen facilitated by K+ recycling through ROMK-1.     

Glucocorticoids enhance the expression of the basolateral Na+:HCO3- cotransporter in renal proximal tubules

BACKGROUND: Studies have shown that glucocorticoids enhance HCO3- reabsorption in proximal tubules. Functional and molecular studies indicate that HCO3- reabsorption in proximal tubules is mediated via luminal H(+)-ATPase and Na+/H+ exchanger (NHE-3), and basolateral Na+:HCO3- cotransporter (NBC) acting in series. The purpose of these experiments was to examine the effect of adrenal steroids on NBC-1 and NHE-3 expression and activity in rat renal proximal tubules. METHODS: Rats were injected subcutaneously with dexamethasone (100 mu/day) or deoxycorticosterone acetate (30 mg/kg), potent glucocorticoid, or mineralocorticoid analogues, respectively. Animals were sacrificed after two or four days, and NBC-1 and NHE-3 mRNA expression and activities were measured in cortex and proximal tubules. RESULTS: Northern hybridizations indicated that cortical NBC-1 mRNA expression increased by approximately 92% in rats treated with dexamethasone for four days (N = 6, P < 0.03) but not two days. NHE-3 mRNA expression remained unchanged. NBC and NHE-3 activities were measured as the Na-dependent pHi recovery from an acid load in the presence or absence of HCO3-, respectively, and appropriate inhibitors in proximal tubule suspensions loaded with BCECF. NBC activity increased by approximately 80% in rats treated with dexamethasone for four days (P < 0.01, N = 5) but not two days. NHE-3 activity increased by 34 and 42% in rats treated with dexamethasone for two and four days, respectively (P < 0.05 and P < 0.02 for each group vs. control). Treatment with deoxycorticosterone acetate did not alter NBC-1 expression. CONCLUSION: Glucocorticoids at pharmacologic concentrations enhance the mRNA expression and functional activity of renal proximal tubule NBC-1. Enhanced NBC and NHE-3 activities could result in increased HCO3- reabsorption in proximal tubule and could contribute to the maintenance of metabolic alkalosis in pathophysiologic states associated with increased glucocorticoid production.     

Multimodal imaging in photic retinopathy

Letter to the Editor     

Delivery of Exogenous miR-124 to Glioblastoma Multiform Cells by Wharton’s Jelly Mesenchymal Stem Cells Decreases Cell Proliferation and Migration,and Confers Chemosensitivity

MicroRNAs (miRs) are potential therapeutic targets in glioblastoma multiforme (GBM), but the difficulties associated with their delivery to tumor target cells have hampered their widespread use. Mesenchymal stem cells (MSCs) can migrate to the sites of cancers, including GBM and exert anti-tumor effects. In this study, it is shown that Wharton’s jelly-MSCs (WJ-MSCs) have the ability to deliver exogenous miRs to GBM cells and the functional impact of this delivery is characterized. It is found that the labeled miR-124, as an example for miR of interest, can be successfully delivered with WJ-MSCs to U87 GBM cells via dependent or exosome-independent processes. It is demonstrated that the delivered exogenous miR-124 significantly decreases the luciferase activity of the target gene CDK6. In addition, the delivered miR-124 enhances the chemosensitivity of GBM cells to temozolomide and decreases the migration of GBM cells. These results suggest that the use of exogenous miRNA delivery with the derived exosomes from WJ-MSCs may provide a novel approach for miRNA replacement therapy in GBM cancers.     

Maternal self-efficacy,postpartum depression,and their relationship with functional status in Iranian mothers

ABSTRACT

Readiness to care for family, infant, and self are important during the postpartum period. The objective of this study was to determine the relationships of self-efficacy and postpartum depressive symptoms with functional status in randomly sampled Iranian mothers (n = 437). The study was cross-sectional and conducted in 2015. The mean (SD) of the total functional status score was 2.3 (0.2) out of a possible score of 1–4. The maximum and minimum scores in infant care were 4.0 and 2.2 and, in social and community activity, levels were 3.5 and 1.0, respectively. Significant inverse correlations were observed between postpartum depressive symptoms and total scores for functional status, self-care, and levels of social and community activity. A significant positive relationship was observed between self-efficacy and functional status and all of its subscales. In the multivariate linear regression model, postpartum depressive symptoms, nulliparity, and low income were significantly negatively related with functional status; maternal self-efficacy, having a spouse aged 26–35 years, high school diploma, lower educational level, and the spouse’s job (shopkeeper) were significantly positively correlated with functional status. Early diagnosis and treatment of depressive symptoms and promotion of maternal self-efficacy may improve overall functional status of mothers in the postpartum.