Effects of probucol in renal function and structure in rats with subtotal kidney ablation.

Probucol is a bisphenolic compound that lowers serum cholesterol and also has potent antioxidant properties. The present studies examined the effects of probucol administration on renal function and structure in a rat model of subtotal renal ablation. After subtotal nephrectomy, rats were fed an isocaloric rat chow diet containing 22.8% protein with or without the addition of 1% probucol. After 4 weeks, clearance studies were performed for determination of glomerular filtration rate (inulin clearance) and effective renal plasma flow (paraaminohippurate clearance). After completion of clearance studies and measurements of arterial blood pressure, the animals were exsanguinated and renal tissue was obtained for histologic evaluation. There were no differences in body weight, hematocrit, and blood pressure between the two groups of rats 4 weeks after subtotal nephrectomy. Rats with a remnant kidney given probucol had a significantly lower serum cholesterol level (47.4 +/- 5.3 mg/dl vs 87.2 +/- 10.4 mg/dl) and urea nitrogen level (40.7 +/- 3.2 mg/dl vs 63.6 +/- 8.1 mg/dl) than the control group. Rats given probucol also had significantly greater values for inulin clearance and clearance of paraaminohippurate and significantly less proteinuria than control rats. Also, rats with a remnant kidney given probucol had a significantly greater number of normal glomeruli (6.2% +/- 2.1% vs 1.1% +/- 0.9%) and a lesser number of severely affected glomeruli, grades III and IV (26.0% +/- 5.9% vs 50.9% +/- 9.1%) than rats with a remnant kidney not given probucol. Tubulointerstitial changes also were significantly less in rats with a remnant kidney given probucol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of Acetazolamide on the Unrinary Excretion of Cyclic AMP and on the Activity of Renal Adenyl Cyclase

Acetazolamide, an inhibitor of the enzyme carbonic anhydrase, increased the urinary excretion of cyclic AMP in normal and parathyroidectomized rats. The increase was greater in rats with intact parathyroid glands than in parathyroidectomized rats. This rise in the urinary excretion of cyclic AMP was not due to an increase in urine flow or a change in urine pH. Furosemide caused an increase in urine flow, but did not affect the excretion of cyclic AMP or phosphate. Alkalinization of the urine with bicarbonate did not increase the urinary excretion of phosphate or cyclic AMP. Acetazolamide increased the productionof cyclic AMP by rat renal cortical slices in vitro. This effect was dose-dependent. Acetazolamide also stimulated the activity of renal cortical adenyl cyclase in a dose-dependent manner but had no effect on the activity of cyclic nucleotide phosphodiesterase. The pattern of urinary excretion of cyclic AMP and phosphate after administration of acetazolamide was similar to that observed in rats given parathyroid hormone. It is suggested that acetazolamide stimulates the renal production of cyclic AMP by activating adenyl cyclase and that this may be the mechanism by which this inhibitor of carbonic anhydrase produces phosphaturia.     

The relative roles of calcium, phosphorus, and parathyroid hormone in glucose- and tolbutamide-mediated insulin release.

The relative contributions of Ca++, phosphorus, and parathyroid hormone (PTH) on insulin secretion were evaluated in three groups of dogs. Dogs were studied with glucose infusions (group I) or standard intravenous glucose tolerance tests (IVGTT) (group II) before and after the development of diet-induced hypophosphatemia. Mean serum phosphorus levels for both groups fell from 4.1 to 1.1 mg/100 ml. Animals in group I demonstrated a fall in glucose disappearance rates (Kg) from 5.3+/-0.6% min to 3.5+/-0.5% after induction of hypophosphatemia (P less than 0.001). Mean insulin response was significantly greater in the hypophosphatemic animals than in controls in this group. In group II animals, mean insulin areas obtained during the IVGTT increased from 1,426+/-223 to 2,561+/-141 muU/ml/60 min after induction of hypophosphatemia, and were unaffected by Ca++ or PTH administration. Ca++ administration, but not hypophosphatemia or PTH infusion, increased significantly the mean insulin response to tolbutamide. Secondary hyperparathyroidism was induced by dietary manipulation in four dogs (group III). Mean PTH values increased from 71.4+/-2.1 to 3,012+/-372 pg/ml (P less than 0.001). Mean insulin response to an IVGTT was similar to group III animals, but increased from 1,352+/-128 to 1,894+/-360 muU/ml/60 min after the excessive dietary phosphorus was reduced for 3 mo, and plasma phosphorus fell from 3.2+/-0.1 to 2.8+/-0.3 mg/100 ml. PTH values decreased to 647+/-53 pg/ml. The insulin response to tolbutamide was comparable to that in group II animals, but increased significantly after calcium administration. Immunoreactive insulin disappearance rates were unaffected by hypophosphatemia or diet-induced secondary hyperparathyroidism. These data demonstrate that hypophosphatemia is associated with an augmented glucose-stimulated insulin release, without any effect on tolbutamide-stimulated insulin release. Hypercalcemia produces an augmented tolbutamide-stimulated insulin release with no apparent effect on glucose-stimulated insulin release. Finally, PTH does not appear to be an insulin antagonist and has no apparent effect on either glucose- or tolbutamide-stimulated insulin release in animals with dietary-induced secondary hyperparathyroidism.     

Relationship between bariatric surgery and periodontal status: a systematic review and meta-analysis

Background

The effects of bariatric surgery can reflect in the oral cavity and can cause alterations in oral health. This high prevalence of oral alterations in the pre and post-operative periods has been highlighted in different studies.

Estrogen-related receptor α in normal adrenal cortex and adrenocortical tumors: Involvement in development and oncogenesis

Aims

The nuclear hormone receptor estrogen-related receptor α (ERRα) regulates the activation of mitochondrial genes in various human tissues, but its role in the adrenal gland and its disorders has not been defined. Therefore, we examined ERRα expression in both normal adrenal cortex (NAC) and adrenocortical tumor (ACT) in order to study the possible correlation of ERRα with adrenal development and tumor development.

Methods

Human adrenal specimens (non-pathological fetal n = 7; non-pathological post-birth n = 40; aldosterone producing adenoma (APA) n = 11; cortisol producing adenoma (CPA) n = 11; adrenocortical carcinoma (ACC) n = 8) were immunohistochemically examined in this study. NAC (n = 13) and ACT (n = 28) frozen tissue specimens were also available for studying ERRα mRNA levels.

Key findings

In fetal NAC tissues, ERRα labeling index (LI) in fetal zone (FZ) was significantly higher that that in neocortex (NC), and the differences among age groups for overall mean LI was statistically significant when analyzed according to individual cortical layers. ERRα LI was also significantly higher in ACC than in other types of ACT. ERRα mRNA was detected in NAC and all types of ACT.

Significance

Results of our present study suggest a possible role of ERRα in adrenal development and ACC.     

Induction of CD14 in tubular epithelial cells during kidney disease

Analysis of gene expression in a mouse model of unilateral ureteral obstruction (UUO) revealed significant induction of CD14 mRNA in kidneys with obstructed ureters. Immunocytochemical analysis indicated that CD14 was upregulated in tubular epithelial cells and this upregulation was not attributable to infiltration of the kidneys by mononuclear cells. This induction of CD14 mRNA was found to occur in BALB/C, C57BL/6, C3H/HeN, and C3H/HeJ mice during UUO. Ischemia/reperfusion of kidneys also induced CD14 mRNA. Mice lacking either of the tumor necrosis factor-alpha receptor (TNFR) genes were also studied; the induction of CD14 was blunted in TNFR 1-knockout mice but not in TNFR2-knockout mice. Apoptosis of tubular cells in lipopolysaccharide-resistant CH3/HeJ mice was significantly (P: < 0. 05) less than that in lipopolysaccharide-responsive CH3/HeN mice during UUO. These results suggest that CD14 is acutely induced in tubular epithelial cells in two mouse models of renal injury. This induction is regulated by tumor necrosis factor-alpha, through TNFR1. CD14 may participate in the apoptosis of tubular epithelial cells on a more chronic basis by activating a pathway that is absent or deficient in C3H/HeJ mice.