Pseudohypoparathyroidism-Ib due to novel heterozygous stop gain mutation in exon 8 of STX16 gene: A case report

We report a case of pseudohypoparathyroidism type 1b (PHP1b) manifesting in childhood with hypocalcemic seizures. Symptomatic hypocalcemia is a common emergency in the pediatric age group with vitamin D deficiency being a frequent underlying etiology and PHP is rare. Patients with PHP1b do not depict the Albright’s hereditary osteodystrophy (AHO) phenotype typical of patients with PHP1a and pseudopseudohypoparathyroidism (PPHP). The resistance to parathyroid hormone (PTH) is documented mostly at renal tubular site of action in patients with PHP1b. Hypothyroidism is reported occasionally, signifying resistance to thyroid-stimulating hormone (TSH). Individuals with autosomal dominant and maternally inherited form of PHP harbor methylation defects at GNAS exon A/B, while sporadic and non-familial cases harbor methylation defects at other locus sites, including differentially methylated regions (GNAS-DMR). A novel heterozygous stop gain mutation c.C910T/p.Arg304X in exon 8 of the STX16 gene (Syntaxin 16) was observed in our case. Resistance seems limited to the renal action of PTH alone as currently, TSH level is normal. Maternal STX16 gene analysis results confirmed the modality of inheritance.

COMPARATIVE INFLUENCE OF TRENTHAL AND XANTHINOL NICOTINATE ON THE FUNCTIONAL STATE OF KIDNEYS IN RATS UNDER CONDITIONS OF SALT LOADING

The aim – to investigate the comparative influence of trenthal and xanthinol nicotinateon the functional state of the rat kidneys under conditions of salt loading after a singleand durable (7 days) administration of preparations.Material and methods. Changes of excretory, water- and ion-regulating functions of thekidneys following a single and long trenthal and xanthinol nicotinate administration atdoses of 3mg/kg under conditions of salt loading with NaCl solution 0,45% were studiedin the experiments on non-linear white rats.Results. Both the rapid response of the kidneys after a single injection of trenthaland xanthinol nicotinate and more significant changes of the renal function followingrepeated (7 days) drugs’ administration under conditions of salt hydration with NaCl0.45% solution were observed. Comparative estimation of the renal action at a singleadministration has shown that xanthinol nicotinate activates water-, ion-regulating andexcretory function of kidneys more significantly than trenthal. After xanthinol nicotinateadministration the urine output in rats increased 74%, natriuresis - 66%, creatinineexcretion – 52% in comparison with the control, while following trenthal administrationthe indices under study increased only 62%, 33% and 34% correspondingly.Under conditions of salt loading water-regulating function of kidneys activated moresignificantly following durable (7 days) administration than after a single introduction ofpreparations. Under trenthal influence diuresis increased 1.8 times, xanthinol nicotinate– 1.9 times in comparison with the control. Trenthal increased endogenous creatinineexcretion – 1.4 times and xanthinol nicotinate – 1.6 times.Natriuresis increased almost 2 times, trenthal - 1.4 times under xanthinol nicotinateinfluence. The natriuretic effect of xanthinol nicotinate is 55% higher than that oftrenthal. Positive correlative relation has been established between increased urinationand natriuresis only after durable xanthinol nicotinate administration (r=0,784, p<0,05).Trenthal appeared to be more pronounced kaliurretic.Conclusions. Excretory, water- and ion-regulating renal function is activated following asingle and protracted (7 days) introduction of methylxanthine derivatives – trenthal andxanthinol nicotinate at a dose of 3mg/kg under hydration conditions with NaCl solution0,45%. Renal effects of the preparations under study is characterized by an increaseof endogenous creatinine excretion. With long-term administration of the preparationsnatriuretic effect predominates in xanthinol nicotinate, kaliuretic effect - in trenthal.

Liver X receptor agonists decrease ENaC-mediated sodium transport in collecting duct cells

Liver X receptors (LXRs) are nuclear receptors that regulate cholesterol, fatty acid, and glucose metabolism in various tissues. However, the renal action of LXRs is not well understood. Here we investigated the effects of LXR-activating ligands on modulation of epithelial sodium channel (ENaC)-mediated sodium transport in collecting duct cells. Exposure of the M1 cells to the synthetic LXR agonists T0901317 and GW3965 or the natural ligand 22R-hydroxycholesterol for 24 h decreased amiloride-sensitive sodium transport, corresponding with an increase of transepithelial resistance. The inhibition of amiloride-sensitive sodium transport after incubation with T0901317 or GW3965 was not mediated by a reduction of Na+/K+-ATPase-mediated basolateral sodium transport. On the other hand, T0901317 and GW3965 decreased mRNA abundance and membrane expression of ENaC. Preincubation the monolayer with GW3965 attenuated aldosterone-induced stimulation sodium transport. In primary cultures of collecting duct cells, T0901317 and GW3965 similarly inhibited ENaC transport function as in M1 cells. This is the first evidence showing LXR-activating ligands modulate ENaC-mediated sodium transport in collecting duct cells. These results suggest that LXRs may represent a novel therapeutic target for treatment of conditions with dysregulation of ENaC such as hypertension.