Type II Bartter's syndrome is a hereditary hypokalemic renal salt-wasting disorder caused by mutations in the ROMK channel (Kir1.1; Kcnj1), mediating potassium recycling in the thick ascending limb of Henle's loop (TAL) and potassium secretion in the distal tubule and cortical collecting duct (CCT). Newborns with Type II Bartter are transiently hyperkalemic, consistent with loss of ROMK channel function in potassium secretion in distal convoluted tubule and CCT. Yet, these infants rapidly develop persistent hypokalemia owing to increased renal potassium excretion mediated by unknown mechanisms. Here, we used free-flow micropuncture and stationary microperfusion of the late distal tubule to explore the mechanism of renal potassium wasting in the Romk-deficient, Type II Bartter's mouse. We show that potassium absorption in the loop of Henle is reduced in Romk-deficient mice and can account for a significant fraction of renal potassium loss. In addition, we show that iberiotoxin (IBTX)-sensitive, flow-stimulated maxi-K channels account for sustained potassium secretion in the late distal tubule, despite loss of ROMK function. IBTX-sensitive potassium secretion is also increased in high-potassium-adapted wild-type mice. Thus, renal potassium wasting in Type II Bartter is due to both reduced reabsorption in the TAL and K secretion by max-K channels in the late distal tubule.

Potassium secretory flux ( J K) by the distal nephron is regulated by systemic and luminal factors. In the present investigation, J K was measured with a double-barreled K+ electrode during paired microperfusion of superficial segments of the rat distal nephron. We used control solutions (100 mM NaCl, pH 7.0) and experimental solutions in which Cl− had been replaced with a less permeant anion and/or pH had been increased to 8.0. J K increased when Cl− was replaced by either acetate (∼37%), sulfate (∼32%), or bicarbonate (∼62%), and also when the pH of the control perfusate was increased (∼26%). The majority (80%) of acetate-stimulated J K was Ba2+sensitive, but furosemide (1 mM) further reduced secretion (∼10% of total), suggesting that K+-Cl− cotransport was operative. Progressive reduction in luminal Cl−concentration from 100 to 20 to 2 mM caused increments in J K that were abolished by inhibitors of K+-Cl− cortransport, i.e., furosemide and [(dihydroindenyl)oxy]alkanoic acid. Increasing the pH of the luminal perfusion fluid also increased J K even in the presence of Ba2+, suggesting that this effect cannot be accounted for only by K+ channel modulation of K+ secretion in the distal nephron of the rat. Collectively, these data suggest a role for K+-Cl− cotransport in distal nephron K+ secretion.

The mental index, mandibular cortical index, and trabecular bone pattern are good parameters for evaluating the effects of RO on severe secondary hyperparathyroidism.

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Panoramic images reveal morphological changes in the jaw bone, indicating likewise changes in the hand/wrist in severe secondary hyperparathyroidism. The severity of the bone changes may be a reflection of the parathyroid hormone levels in advanced chronic kidney disease.

Amorim, José B. O., and Gerhard Malnic. V 1 receptors in luminal action of vasopressin on distal K ϩ secretion. Am J Physiol Renal Physiol 278: F809-F816, 2000.-Luminal perfusion with collected proximal fluid increases distal K ϩ secretion compared with artificial solutions. Arginine vasopressin (AVP), present in luminal fluid, might be responsible for this observation. K ϩ secretion rate (J K ) was measured by K ϩ -sensitive microelectrodes during paired luminal stationary microperfusion with control and AVP-containing 0.5 mM K ϩ solutions. J K was 1.34 Ϯ 0.35 (n ϭ 24 tubules) nmol · cm Ϫ2 ·s Ϫ1 during perfusion with 10 Ϫ9 M AVP, against 0.90 Ϯ 0.12 nmol · cm Ϫ2 ·s Ϫ1 (n ϭ 21) in control (P Ͻ 0.02). With 10 Ϫ9 M AVPϩ10 Ϫ6 M ␤-mercapto-␤-␤-cyclopenta-methylenepropionyl 1 , O-Me-Tyr 2 -Arg 8 vasopressin (MCMV), a specific peptide V 1 -receptor antagonist, J K was 0.36 Ϯ 0.067 against 0.77 Ϯ 0.10 (control; n ϭ 9) nmol · cm Ϫ2 ·s Ϫ1 (P Ͻ 0.01). With 10 Ϫ6 M MCMV alone, J K was 0.37 Ϯ 0.04 against a control of 0.62 Ϯ 0.06 (n ϭ 19) nmol · cm Ϫ2 ·s Ϫ1 (P Ͻ 0.01). A peptide V 2 antagonist had no such effect. In Brattleboro rats, which do not produce endogenous AVP, MCMV had no effect when given alone, although AVP still stimulated J K . In conclusion, luminal AVP stimulates distal J K significantly. The V 1 antagonist MCMV inhibits the effect of AVP but also reduces J K when given alone. This suggests that AVP acts luminally via V 1 receptors but also that there appears to be a background effect of endogenous AVP blocked by the antagonist. potassium; anti-V 1 ; distal tubule; microperfusion IT HAS BEEN NOTED THAT DURING free-flow micropuncture experiments in cortical distal tubules, ''in vivo'' K ϩ secretion at a given flow rate is considerably higher than during microperfusion with artificial Ringer solutions (23,26). It is well known that distal K ϩ secretion is a function of flow rate, distal sodium load, pH. and transepithelial potential difference (PD), among other factors (14, 43). However, it has also been shown that during distal perfusion with native proximal fluid collected before the experiment, distal K ϩ secretion is markedly higher than when an artificial Ringer solution of comparable composition is perfused (27). This finding suggested the presence, in native proximal fluid, of endocrine or paracrine factors that might stimulate this transport process by acting at the luminal surface of tubule cells. A similar suggestion has been made for fluid and sodium reabsorption in proximal tubule (19).In the present work, we have investigated the role of arginine vasopressin (AVP) in distal K ϩ secretion. AVP is a peptide hormone that has been found to affect this process and is present in luminal fluid in physiological conditions (6,21). Vasopressin has been shown by several groups to stimulate K ϩ secretion in cortical distal tubule (9, 12) and in cortical collecting duct (8,35,41) and is found in final urine in significant concentrations (21). ADH action on K ϩ secretion has been found mostly in rat cortical co...

Background There are many comorbidities associated with Down syndrome (DS), including obstructive sleep apnea (OSA) and masticatory muscle alteration. Muscular hypotonia, in particular, of the masticatory and oropharyngeal muscles is one of the main characteristics of individuals with DS, resulting in impairments of speech, swallowing, and mastication in these individuals. In addition, total or partial obstruction of the airways during sleep can occur due to pharyngeal hypotonia, leading to snoring and to OSA. This progressive respiratory disorder is associated with a high risk of morbidity and mortality in individuals with DS. The aim of this research is to assess the therapeutic effects of surface neuromuscular electrical stimulation (NMES), the mastication apparatus (MA), and a mandibular advancement oral appliance (OA m ) with an embedded thermosensitive microchip on the functions of masticatory muscles (bilateral masseter and temporal muscles), physiological sleep variables, and salivary parameters in adult patients with DS. Methods The patients with DS will be randomly selected and divided into three groups (DS-NMES, DS-MA, and DS-OA m ) with a minimum of 10 patients in each group. A thermosensitive microchip will be embedded in the OA m to record its compliance. The therapeutic effects on masticatory muscle function will be investigated through electromyography, a caliper, and a force-transducer device; the sleep variables, in turn, will be evaluated by means of polysomnography. The physicochemical and microbiological properties of the saliva will also be analyzed, including the salivary flow, viscosity, buffer capacity, cortisol levels (susceptibility to psychological and/or physical stress), and Pseudomonas aeruginosa levels (risk of aspiration pneumonia) in these patients. The methods determined for this study will be carried out prior to and after 2 months of the recommended therapies. Discussion The primary outcomes would be the improvement and/or reestablishment of the function of masticatory muscles and the physiological sleep variables in this target public since individuals with DS commonly present generalized muscular hypotonia and dysfunction of the oropharyngeal musculature. As a secondary outcome indicator, the impact of the applied therapies (NMES, MA, and OA m ) on the salivary microbiological and physicochemical properties in DS individuals will also be assessed. Furthermore, the compliance of OA m usage will be measured through a thermosensitive microchip. Trial registration Registro Brasileiro de Ensaios Clínicos, RBR-3qp5np . Registered on 20 February 2018. Electronic supplementary material The online version of this article (10.1186/s13063-019-3300-0) cont...

Ectodermal dysplasia (ED) is a rare hereditary disorder affecting the development of ectoderm-derived organs and tissues. The aim of this study was to describe phenotypic features and the therapeutic approach in dentistry among three patients with ED, correlating their data with the literature. Additionally, to investigate the salivary gland disorders and their impacts on oral microbiota, we performed salivary tests, including salivary flow rate, salivary buffering capacity, and concentration levels of mutans streptococci, lactobacilli, and yeasts. All patients presented oligodontia, resulting in a significant masticatory dysfunction and aesthetic impairment. The counts of mutans streptococci (n=3) and yeasts (n=2) were high; on the other hand, the count of lactobacilli (n=3) was low. Therefore, salivary and microbiological tests showed that the patients with ED, particularly the hypohidrotic type, presented a high risk of enamel caries and susceptibility to oral infections, which may be likely triggered by reduction of salivary flow and/or possible immunological disorders.