Functional expression of electrogenic sodium bicarbonate cotransporter 1 (NBCe1) in mouse cortical astrocytes is dependent on S255-257 and regulated by mTOR.

The electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), is the major bicarbonate transporter expressed in astrocytes. It is highly sensitive for bicarbonate and the main regulator of intracellular, extracellular, and synaptic pH, thereby modulating neuronal excitability. However, despite these essential functions, the molecular mechanisms underlying NBCe1-mediated astrocytic response to extracellular pH changes are mostly unknown. Using primary mouse cortical astrocyte cultures, we investigated the effect of long-term extracellular metabolic alkalosis on regulation of NBCe1 and elucidated the underlying molecular mechanisms by immunoblotting, biotinylation of surface proteins, intracellular H+ recording using the H+ -sensitive dye 2',7'-bis-(carboxyethyl)-5-(and-6)-carboxyfluorescein, and phosphoproteomic analysis. The results showed significant downregulation of NBCe1 activity following metabolic alkalosis without influencing protein abundance or surface expression of NBCe1. During alkalosis, the rate of intracellular H+ changes upon challenging NBCe1 was decreased in wild-type astrocytes, but not in cortical astrocytes from NBCe1-deficient mice. Alkalosis-induced decrease of NBCe1 activity was rescued after activation of mTOR signaling. Moreover, mass spectrometry revealed constitutively phosphorylated S255-257 and mutational analysis uncovered these residues being crucial for NBCe1 transport activity. Our results demonstrate a novel mTOR-regulated mechanism by which NBCe1 functional expression is regulated. Such mechanism likely applies not only for NBCe1 in astrocytes, but in epithelial cells as well.

Insulin infusion responses in diabetic ketoacidosis alone and with a mixed hypochloremic alkalosis.

AIMS: Although diabetic ketoacidosis (DKA) commonly presents as a pure diabetic ketoacidosis (PDKA), up to 30% of cases may be associated with a mixed hypochloremic metabolic alkalosis (HMA). It is unknown whether there is a difference in treatment outcomes between these two entities. We evaluated an insulin infusion protocol (IIP), previously validated for hyperglycemia management in ICU's, for the management of PDKA and HMA. MATERIALS AND METHODS: A retrospective case series/cohort study of 41 DKA admissions was further characterized as having PDKA or HMA. HMA was defined in those having an elevated delta-delta gradient (ΔAG-ΔHCO3) ≥ 5 mmol/L and base excess chloride (BECl) > 2.7 mmol/L. The main outcome measures were times to recovery of glucose levels to ≤250 mg/dL and of anion gap to ≤12 mmol/L. RESULTS: The initial serum glucose was 553 ±â€¯265 mg/dL, serum bicarbonate of 8.8 ±â€¯5.1 mmol/L, and venous pH 7.13 ±â€¯0.2). Recovery of glucose occurred in 5 h: 25 min (±3 h:39min), and for anion gap in 11 h:25 min (±6 h:56min). HMA compared with PDKA had a delayed recovery of serum glucose (7 h: 23min ±â€¯3 h: 35min vs. 4 h: 31min ±â€¯3:h:21min, p = 0.017), which was due to the higher initial level of glucose (p = 0.02) rather than level of BECl (p = 0.17). There was no difference in time to anion gap closure between the PDKA and HMA. CONCLUSIONS: Correction of hyperglycemia and acidosis in PDKA as well as in HMA was managed through the IIP. The simultaneous fluid and electrolyte management corrected the hypochloremic alkalosis.

Downregulation of the Cl-/HCO3-Exchanger Pendrin in Kidneys of Mice with Cystic Fibrosis: Role in the Pathogenesis of Metabolic Alkalosis.

BACKGROUND/AIMS: Patients with cystic fibrosis (CF) are prone to the development of metabolic alkalosis; however, the pathogenesis of this life threatening derangement remains unknown. We hypothesized that altered acid base transport machinery in the kidney collecting duct underlies the mechanism of impaired bicarbonate elimination in the CF kidney. METHODS: Balance studies in metabolic cages were performed in WT and CFTR knockout (CF) mice with the intestinal rescue in response to bicarbonate loading or salt restriction, and the expression levels and cellular distribution of acid base and electrolyte transporters in the proximal tubule, collecting duct and small intestine were examined by western blots, northern blots and/or immunofluorescence labeling. RESULTS: Baseline parameters, including acid-base and systemic vascular volume status were comparable in WT and CF mice, as determined by blood gas, kidney renin expression and urine chloride excretion. Compared with WT animals, CF mice demonstrated a significantly higher serum HCO3- concentration (22.63 in WT vs. 26.83 mEq/l in CF mice; n=4, p=0.013) and serum pH (7.33 in WT vs. 7.42 in CF mice; n=4, p=0.00792) and exhibited impaired kidney HCO3- excretion (urine pH 8.10 in WT vs. 7.35 in CF mice; n=7, p=0.00990) following a 3-day oral bicarbonate load. When subjected to salt restriction, CF mice developed a significantly higher serum HCO3- concentration vs. WT animals (29.26 mEq/L in CF mice vs. 26.72 in WT; n=5, p=0.0291). Immunofluorescence labeling demonstrated a profound reduction in the apical expression of the Cl-/HCO3- exchanger pendrin in cortical collecting duct cells and western and northern blots indicated diminished plasma membrane abundance and mRNA expression of pendrin in CF kidneys. CONCLUSIONS: We propose that patients with cystic fibrosis are prone to the development of metabolic alkalosis secondary to the inactivation of the bicarbonate secreting transporter pendrin, specifically during volume depletion, which is a common occurrence in CF patients.

Respuesta a la carta en relación con el editorial: Sabate A, Koo M. Intravenous fluids: Concepts and rationality of use. Cir Esp. 2016;94:369-371 / The authors reply: in relation to the editorial: Sabate A, Koo M. Intravenous fluids: Concepts and rationality of use. Cir Esp. 2016;94:369-371

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Implications of a pre-exercise alkalosis-mediated attenuation of HSP72 on its response to a subsequent bout of exercise.

The aim of this study was to investigate if a pre-exercise alkalosis-mediated attenuation of HSP72 had any effect on the response of the same stress protein after a subsequent exercise. Seven physically active males [25.0 ± 6.5 years, 182.1 ± 6.0 cm, 74.0 ± 8.3 kg, peak aerobic power (PPO) 316 ± 46 W] performed a repeated sprint exercise (EXB1) following a dose of 0.3 g kg(-1) body mass of sodium bicarbonate (BICARB), or a placebo of 0.045 g kg(-1) body mass of sodium chloride (PLAC). Participants then completed a 90-min intermittent cycling protocol (EXB2). Monocyte expressed HSP72 was significantly attenuated after EXB1 in BICARB compared to PLAC, however, there was no difference in the HSP72 response to the subsequent EXB2 between conditions. Furthermore there was no difference between conditions for measures of oxidative stress (protein carbonyl and HSP32). These findings confirm the sensitivity of the HSP72 response to exercise-induced changes in acid-base status in vivo, but suggest that the attenuated response has little effect upon subsequent stress in the same day.

Causa inusual d'obstrucció gàstrica en el lactant: membrana antropilòrica / Causa inusual de obstrucción gástrica en el lactante: membrane antropilórica / Unusual cause of gastric outlet obstruction in infants; antral web

Introducció: la membrana antropilòrica (MA) és una alteració congènita de baixa incidència i difícil diagnòstic per la seva semblança clinicoradiològica amb l'estenosi hipertròfica de pílor (EHP). La MA completa o parcial causa una obstrucció del buidament gàstric que provoca vòmits de repetició no biliosos, deshidratació, pèrdua de pes i alcalosi metabòlica hipoclorèmica. La radiografia d'abdomen mostra una dilatació gàstrica greu, i l'ecografia abdominal ens descarta l'EHP. Aleshores cal plantejar altres causes d'obstrucció a la sortida gàstrica en el lactant, com la MA. Cas clínic: es presenta el cas d'un lactant d'1 mes i 5 dies, sense antecedents obstètrics d'interès, que consulta per vòmits no biliosos, estancament ponderal i hipotonia de 24 hores d'evolució. Les exploracions complementàries fetes van ser normals, tret d'un lleu reflux gastroesofàgic, i es va descartar l'EHP per ecografia abdominal. Davant la sospita d'intolerància a proteïnes de llet de vaca es va fer un canvi de fórmula d'inici a fórmula elemental amb persistència de la clínica i instauració progressiva d'alcalosi metabòlica. Amb la sospita de MA, es va fer un segon estudi ecogràfic dirigit que mostrava un petit ressort antropilòric que es va confirmar en la fibrogastroscòpia, i es va diagnosticar una MA parcial. La resecció quirúrgica de la membrana va re-soldre la clínica. Comentaris: davant d'un lactant amb obstrucció gàstrica, i un cop descartada la causa més comú (EHP), cal pensar en la membrana antral com a possible etiologia, ja que si aquesta es confirma, el seu maneig quirúrgic és definitiu amb resolució clínica posterio

Introducción. La membrana antropilórica (MA) es una alteración de baja incidencia y difícil diagnóstico por el parecido clínico-radiológico con la estenosis hipertrófica de píloro (EHP). La MA completa o parcial causa una obstrucción en la salida gástrica produciendo vómitos de repetición no biliosos, deshidratación, pérdida de peso y alcalosis metabólica hipoclorémica. La radiografía de abdomen muestra una dilatación gástrica severa y la ecografía abdominal descarta la EHP. Es entonces cuando hemos de plantear otras causas de obstrucción de la salida gástrica en el lactante, como la MA. Caso clínico. Se presenta el caso de un lactante de 1 mes y 5 días, sin antecedentes obstétricos de interés, que consulta por vómitos no biliosos, estancamiento ponderal e hipotonía de 24 horas de evolución. Las exploraciones complementarias realizadas fueron normales, excepto un leve reflujo gastroesofágico, y se descartó la EHP por ecografía abdominal. Ante la sospecha de intolerancia a proteínas de leche de vaca se realizó un cambio de fórmula de inicio a fórmula elemental, con persistencia de la clínica e instauración progresiva de alcalosis metabólica. Con la sospecha de MA, se realizó un segundo estudio ecográfico dirigido que mostraba un pequeño resorte antropilórico que se confirmaba en la fibrogastroscopia, y se diagnosticó una MA parcial. Con la resección quirúrgica de la membrana se resolvió la clínica. Comentarios. Ante un lactante con obstrucción gástrica, y una vez descartada la causa más común (EHP), se ha de pensar en la membrana antral como posible etiología, ya que si esta se confirma, su manejo quirúrgico es definitivo con la resolución clínica posterior (AU)

Introduction. The antral web (AW) is a disorder of low incidence and difficult diagnosis despite its similar clinical and radiological findings to hypertrophic pyloric stenosis (HPS). Complete or partial AW cause gastric outlet obstruction with persistent non-bilious vomiting, dehydration, weight loss, and hypochloremic metabolic alkalosis. Abdominal radiograph shows severe gastric dilatation; however, the normal abdominal ultrasound ruling out HPS should raise the suspicion of other causes of gastric outlet obstruction, such as AW. Case report. We report a case of a one-month and five days-old infant with no relevant obstetric history, who presented with a 24- hour history of non-bilious vomiting, lack of weight gain and hypotonia. Diagnostic studies suggested mild gastroesophageal reflux, and an abdominal ultrasound ruled out HPS. The diagnosis of intolerance to cow’s milk protein was first considered, and elemental formula was started without improvement. Suspecting AW, a repeat abdominal ultrasound showed a small prepyloric spring. Gastroscopy confirmed the diagnosis of partial AW, and surgical resection of the membrane resulted in resolution of the symptoms. Comments. In the presence of an infant with gastric outlet obstruction syndrome, and after the most common cause (HPS) has been ruled out, the diagnosis of AW should be considered. Surgery is curative (AU)

Carbonic anhydrase inhibitors and high altitude illnesses.

Carbonic anhydrase (CA) inhibitors, particularly acetazolamide, have been used at high altitude for decades to prevent or reduce acute mountain sickness (AMS), a syndrome of symptomatic intolerance to altitude characterized by headache, nausea, fatigue, anorexia and poor sleep. Principally CA inhibitors act to further augment ventilation over and above that stimulated by the hypoxia of high altitude by virtue of renal and endothelial cell CA inhibition which oppose the hypocapnic alkalosis resulting from the hypoxic ventilatory response (HVR), which acts to limit the full expression of the HVR. The result is even greater arterial oxygenation than that driven by hypoxia alone and greater altitude tolerance. The severity of several additional diseases of high attitude may also be reduced by acetazolamide, including high altitude cerebral edema (HACE), high altitude pulmonary edema (HAPE) and chronic mountain sickness (CMS), both by its CA-inhibiting action as described above, but also by more recently discovered non-CA inhibiting actions, that seem almost unique to this prototypical CA inhibitor and are of most relevance to HAPE. This chapter will relate the history of CA inhibitor use at high altitude, discuss what tissues and organs containing carbonic anhydrase play a role in adaptation and maladaptation to high altitude, explore the role of the enzyme and its inhibition at those sites for the prevention and/or treatment of the four major forms of illness at high altitude.

Cortical GABAergic neurons are more severely impaired by alkalosis than acidosis.

BACKGROUND: Acid-base imbalance in various metabolic disturbances leads to human brain dysfunction. Compared with acidosis, the patients suffered from alkalosis demonstrate more severe neurological signs that are difficultly corrected. We hypothesize a causative process that the nerve cells in the brain are more vulnerable to alkalosis than acidosis. METHODS: The vulnerability of GABAergic neurons to alkalosis versus acidosis was compared by analyzing their functional changes in response to the extracellular high pH and low pH. The neuronal and synaptic functions were recorded by whole-cell recordings in the cortical slices. RESULTS: The elevation or attenuation of extracellular pH impaired these GABAergic neurons in terms of their capability to produce spikes, their responsiveness to excitatory synaptic inputs and their outputs via inhibitory synapses. Importantly, the dysfunction of these active properties appeared severer in alkalosis than acidosis. CONCLUSIONS: The severer impairment of cortical GABAergic neurons in alkalosis patients leads to more critical neural excitotoxicity, so that alkalosis-induced brain dysfunction is difficultly corrected, compared to acidosis. The vulnerability of cortical GABAergic neurons to high pH is likely a basis of severe clinical outcomes in alkalosis versus acidosis.

Gitelman's syndrome with vomiting manifested by severe metabolic alkalosis and progressive renal insufficiency.

Gitelman's syndrome is an autosomal recessive salt-losing tubulopathy showing hypokalemic hypomagnesemic hypocalciuria with metabolic alkalosis and hyperreninemic hyperaldosteronism. This syndrome is caused by mutations in the SLC12A3 gene that encodes sodium-chloride cotransporter expressed at the apical membrane of renal distal convoluted tubule. Symptoms and renal outcomes of Gitelman's syndrome are, in general, mild and benign, and renal insufficiency from Gitelman's syndrome associated with long-standing hypokalemia and volume depletion is extremely rare. Herein, we report a 27-year-old male patient with Gitelman's syndrome who manifested renal failure, hypokalemia, severe metabolic alkalosis and altered mentality. About one year ago, the patient had been transferred to Seoul National University Hospital, because of unsolved hypokalemia, and was diagnosed as Gitelman's syndrome by clinical features and genetic analysis of the SLC12A3 gene. The patient carries a missense mutation at one allele of SLC12A3 gene (c.781C>T, p.Arg261Cys). His mother is also heterozygous for the same mutation and she had a history of hypokalemia. On this admission, the patient had recurrent bouts of vomiting induced by psychiatric eating disorder and showed severe volume depletion with hypotension, azotemia and metabolic alkalosis. Intense hydration therapy and emergency hemodialysis transiently improved his fluid-electrolyte imbalance and renal function. However, renal dysfunction progressively deteriorated despite the medical treatment. Our findings suggest that even in Gitelman's syndrome, constant monitoring for volume status and other comorbid conditions should be employed to prevent progressive renal injury.

Effects of extracellular acidic-alkaline stresses on trigeminal ganglion neurons in the mouse embryo in vivo.

Acidic-alkaline stresses caused by ischemia and hypoglycemia induce neuronal cell death resulting from intracellular pH disturbance. The effects of acidic-alkaline disturbance on the trigeminal ganglion (TG) neurons of the embryonic mouse were investigated by caspase-3-immunohistochemistry and Nissl staining. TG neurons exhibited apoptosis in 3.08 ± 0.55% of neurons in intact embryos at day 16. Intraperitoneal injection of alkaline solution (pH 8.97; 0.005-0.1 M K2HPO4 or 0.01-0.04 M KOH) into the embryo at embryonic day 15 significantly increased the number of apoptotic neurons in the TG at embryonic day 16 with dependence on concentration (3.40-6.05 and 2.93-5.55%, respectively). On the other hand, acidic solutions (pH 4.4; 0.01-0.2 M KH2PO4 slightly, but not significantly, increased the number of apoptotic cells (3.64-5.15%, without dependence on concentration). Neutral solutions (pH 7.4; 0.01-0.2 M potassium phosphate buffer) had no effect on neuronal survival in the TG (2.89-3.48%). The results indicated that alkaline stress significantly increased apoptosis in the developing nervous system, but acidic stress did not.

Adaptation to alkalosis induces cell cycle delay and apoptosis in cortical collecting duct cells: role of Aquaporin-2.

Collecting ducts (CD) not only constitute the final site for regulating urine concentration by increasing apical membrane Aquaporin-2 (AQP2) expression, but are also essential for the control of acid-base status. The aim of this work was to examine, in renal cells, the effects of chronic alkalosis on cell growth/death as well as to define whether AQP2 expression plays any role during this adaptation. Two CD cell lines were used: WT- (not expressing AQPs) and AQP2-RCCD(1) (expressing apical AQP2). Our results showed that AQP2 expression per se accelerates cell proliferation by an increase in cell cycle progression. Chronic alkalosis induced, in both cells lines, a time-dependent reduction in cell growth. Even more, cell cycle movement, assessed by 5-bromodeoxyuridine pulse-chase and propidium iodide analyses, revealed a G2/M phase cell accumulation associated with longer S- and G2/M-transit times. This G2/M arrest is paralleled with changes consistent with apoptosis. All these effects appeared 24 h before and were always more pronounced in cells expressing AQP2. Moreover, in AQP2-expressing cells, part of the observed alkalosis cell growth decrease is explained by AQP2 protein down-regulation. We conclude that in CD cells alkalosis causes a reduction in cell growth by cell cycle delay that triggers apoptosis as an adaptive reaction to this environment stress. Since cell volume changes are prerequisite for the initiation of cell proliferation or apoptosis, we propose that AQP2 expression facilitates cell swelling or shrinkage leading to the activation of channels necessary to the control of these processes.

[Complex metabolic disorders revealing a gastric ulcer of the bulb. A case report]. / Troubles métaboliques complexes révélateurs d'un ulcère gastrique sténosant du bulbe. A propos d'un cas.

We report the case of a 54-year-old man, without particular pathological antecedents admitted to the emergency of the university hospital of Monastir, for right renal colic. Radiography of the urinary tract without preparation and renal echography showed bilateral renal lithiasis and a right ureteral lithiasis. The interrogation revealed concept of vomiting after which the patient felt relieved. The biological assessment objectified an hypochloremic metabolic alcalosis, an increase in the anion gap, a severe impaired renal function of obstructive origin and an hypokaliemia. The presence of the lithiasis did not explain on its own the metabolic disorders of this patient. The other investigations showed that initial pathology was an evolutionary bulb ulcer into pre-stenosis justifying treatment by omeprazole and explaining the biological disorders.

Alcalosis metabólica de origen dietético en un lactante / Infant metabolic alkalosis of dietetic origin

La alcalosis metabólica (AlcM) puede ser sensible o resistente al tratamiento con cloruro sódico en función de su respuesta a éste. La AlcM resistente presenta elevada excreción urinaria de cloro y es secundaria a tubulopatías o al uso de diuréticos; la AlcM sensible incluye vómitos, fibrosis quística y déficit de ingesta. A continuación se presentan los casos de 2 lactantes alimentadas con leche de almendras que presentaron deshidratación y fallo de medro. En ambos casos se observó AlcM hipoclorémica e hipopotasémica, que respondió satisfactoriamente a la reposición hidroelectrolítica. Tras descartar vómitos, ingesta de fármacos, tubulopatías y fibrosis quística se llegó al diagnóstico de déficit en la ingesta debido al escaso aporte de cationes sodio (Na+) y aniones cloro (Cl−) que proporciona la leche de almendras. Este déficit induce un incremento de la reabsorción tubular proximal del anión bicarbonato, y en las porciones distales de la nefrona induce un aumento de la reabsorción de Na+ y Cl−, que se intercambian con cationes potasio y cationes hidrógeno, lo que favorece la aparición de alcalosis hipoclorémica e hipopotasémica. Asimismo, en uno de los casos se constató hipotiroidismo secundario (aparentemente debido al nulo aporte de yodo de la leche de almendras) y trastorno de la mielinización caracterizado por neuritis óptica e hipoacusia. Estos trastornos se resolvieron al administrar una alimentación con fórmula humanizada (AU)

Cases of metabolic alkalosis are divided into susceptible or resistant to treatment with sodium chloride, depending on the response to it. The resistant cases present with high urinary excretion of chloride, and are secondary to tubular disease or use of diuretics. Included among the sensitive cases are, vomiting, cystic fibrosis and low intake. Two infants were fed with “almond milk” and showed clinical symptoms of dehydration and failure to thrive. Hypochloraemic and hypokalaemic metabolic alkasosis was seen in both cases, which responded satisfactorily to water and electrolyte replacement. After ruling out vomiting, ingestion of drugs, tubular disease, and cystic fibrosis, the diagnosis was low intake, due to poor contribution of Na+ and Cl− provided by the “almond milk”. This deficit induces an increase in proximal tubular reabsorption of H−CO3 and in parts of the distal nephron, an increase in reabsorption of Na+ and Cl− which are exchanged with K+ and H+, which can give rise to a hypochloraemic alkalosis and hypokalaemia. Secondary hypothyroidism was found in one case, apparently due to the lack of iodine in the almond milk, and disorders of the myelination characterized by optic neuritis and hearing loss. These disorders were resolved when feeding with human formula was established (AU)

[Pathological changes of potential-activated calcium channels in sensory neurons].

The review considers the structure and function of high-and low-voltage potential activated calcium channels in sensory neurons. A special attention is paid to compression of the function of these channels in normal conditions and during development of pathological conditions. The role of low-voltage activated T-type calcium channels during such forms of pathology as neuropathy, acidosis and alkalosis because the changes in synaptic transmission occurring during these forms of pathological changes are most intensively altered during changes in functional structures of these type of channels. During studying of high-voltage activated calcium channels main attention has been concentrated on changes in the function of N-type potential activated calcium channels.

MAPK signaling pathways are needed for survival of H9c2 cardiac myoblasts under extracellular alkalosis.

pH is one of the most important physiological parameters, with its changes affecting the function of vital organs like the heart. However, the effects of alkalosis on the regulation of cardiac myocyte function have not been extensively investigated. Therefore, we decided to study whether the mitogen-activated protein kinase (MAPK) signaling pathways [c-Jun NH2-terminal kinases (JNKs), extracellular signal-regulated kinases (ERKs), and p38 MAPK] are activated by alkalosis induced with Tris-Tyrode buffer at two pH values, 8.5 and 9.5, in H9c2 rat cardiac myoblasts. These buffers also induced intracellular alkalinization comparable to that induced by 1 mM NH4Cl. The three MAPKs examined presented differential phosphorylation patterns that depended on the severity and the duration of the stimulus. Inhibition of Na+/H+ exchanger (NHE)1 by its inhibitor HOE-642 prevented alkalinization and partially attenuated the alkalosis (pH 8.5)-induced activation of these kinases. The same stimulus also promoted c-Jun phosphorylation and enhanced the binding at oligonucleotides bearing the activator protein-1 (AP-1) consensus sequence, all in a JNK-dependent manner. Additionally, mitogen- and stress-activated kinase 1 (MSK1) was transiently phosphorylated by alkalosis (pH 8.5), and this was abolished by the selective inhibitors of either p38 MAPK or ERK pathways. JNKs also mediated Bcl-2 phosphorylation in response to incubation with the alkaline medium (pH 8.5), while selective inhibitors of the three MAPKs diminished cell viability under these conditions. All these data suggest that alkalosis activates MAPKs in H9c2 cells and these kinases, in turn, modify proteins that regulate gene transcription and cell survival.

Liddle syndrome in a newborn infant.

A 10-week-old female infant developed hypertension. The elevated blood pressure was associated with metabolic alkalosis and urinary chloride wastage. The family history was unremarkable. Her urinalysis, blood urea nitrogen (BUN), and serum creatinine concentrations were all normal. A renal ultrasound was normal. A technetium-99m diethylenetriaminopentoacetic acid (DTPA) renal scan with captopril showed normal blood flow bilaterally. The head ultrasound and echocardiogram were normal. Blood epinephrine, norepinephrine, catecholamines, thyroxine, and steroid levels were also normal. Treatment with various combinations of labetalol, hydralazine, captopril, methyldopa, nifedipine, and spironolactone, all at high doses, failed to control the elevated blood pressure. Serum aldosterone level and peripheral plasma renin activity were low. The lack of therapeutic response to spironolactone, with a good response to amiloride and recurrence of hypertension and metabolic alkalosis after amiloride cessation that was subsequently treated with amiloride, established the diagnosis of Liddle syndrome. To our knowledge, this is the youngest patient with Liddle syndrome that has been reported in the literature.

Choroidal calcifications in patients with Gitelman's syndrome.

Gitelman's syndrome is a renal tubular disorder characterized by a sodium and chloride reabsorption defect in distal tubular cells that determines hypokalemia, metabolic alkalosis, hypomagnesemia, and low calcium excretion. The presence of choroidal calcifications was sought in five patients with Gitelman's syndrome by ophthalmic examination, fluorescein angiography, indocyanine green angiography, and ocular ultrasonography. Calcifications observed in the choroid of two patients were shown by ultrasonography in both patients. Ophthalmic and fluorangiographic examinations detected this alteration in one of the two subjects. Chondrocalcinosis was found in one patient with choroidal calcifications. These findings suggest that precipitation of calcium salts can occur in the choroidal tissue of patients with Gitelman's syndrome. Deposits appeared to be well seen by ultrasonography because of their depth in ocular tissues. Sclerochoroidal calcifications may be favored by the low calcium excretion, which is associated with normal intestinal calcium absorption in patients with Gitelman's syndrome.