Bone mineral density and growth changes in patients with distal renal tubular acidosis after two-years treatment with a new alkalizing drug (ADV7103) / Cambios en la densidad mineral ósea y en el crecimiento en pacientes con acidosis tubular renal distal tras dos años de tratamiento con un nuevo fármaco alcalinizante (ADV7103)

Background and objectives: ADV7103 is a new prolonged-release treatment for distal renal tubular acidosis (dRTA), containing potassium citrate and potassium bicarbonate. Since acidosis may affect bone mineral contents, the effects of ADV7103 on bone mineral density (BMD) and growth in patients with dRTA over 24 months were evaluated. Patients and methods: Thirty patients (24 paediatric patients and 6 adults) were included in an open-label extension study after a phase II/III trial. BMD, measured by densitometry, was assessed at baseline and at 24 months. Growth was evaluated throughout the study. Plasma bicarbonate, parathyroid hormone, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, bone alkaline phosphatase, calciuria and citraturia, were also determined. Safety and treatment compliance were evaluated as well. Results: After 24 months of treatment with ADV7103, mean spine BMD z-score values significantly increased as compared with baseline (p=0.024). In adults, spine and whole-body densitometry z-scores showed a significant correlation with plasma bicarbonate levels (rS=0.82 and rS=0.97, respectively, p<0.005). There was an increase>0.5 units in z-scores for height and weight in 18% and 36% of the paediatric patients, respectively. With treatment, plasma bicarbonate concentration and calciuria at the different visits were normal in 69–86% and 93–96% patients, respectively. Only nine treatment-related gastrointestinal AEs of mild/moderate severity, were reported in five patients. Conclusions: Two years of ADV7103 treatment improved growth and increased spine BMD. These results suggest that control of acidosis by ADV7103 treatment improves bone parameters. (AU)

Antecedentes y objetivo: El ADV7103 es un nuevo tratamiento de liberación prolongada para la acidosis tubular renal distal (ATRd), que contiene citrato potásico y bicarbonato potásico. Dado que la acidosis puede afectar al contenido mineral óseo, se ha evaluado el efecto de dicho medicamento a lo largo de 24 meses sobre la densidad mineral ósea (DMO) y el crecimiento en pacientes con ATRd. Pacientes y métodos: Se incluyeron treinta pacientes (24 pediátricos y seis adultos) en un estudio abierto de extensión tras un ensayo clínico de fase II/III. La DMO medida por densitometría se midió al inicio del estudio y los 24 meses. El crecimiento se evaluó a lo largo del estudio. Adicionalmente, se determinaron el bicarbonato plasmático, la parathormona, 25 hidroxivitamina D, 1,25 dihidroxivitamina D, fosfatasa alcalina ósea, calciuria y citraturia. La seguridad y el cumplimento terapéutico también fueron evaluados. Resultados: Tras 24 meses de tratamiento con ADV7103 la media del z-score de DMO de columna aumentó significativamente frente al valor basal (p = 0,024). En los adultos el z-score de la densitometría de columna y corporal total mostró una correlación significativa con los valores de bicarbonato plasmático (rS = 0,82 y rS = 0,97, respectivamente, p < 0,005). Se registró un incremento > 0,5 unidades de z-score para altura y peso en el 18 y 36%, respectivamente, de los pacientes pediátricos. Con el tratamiento, la concentración plasmática de bicarbonato y la calciuria fueron normales en las diferentes visitas en un 69-86% y un 93-96% de los pacientes, respectivamente. Solamente se notificaron nueve eventos adversos gastrointestinales relacionados con el tratamiento, todos de intensidad leve/moderada en cinco pacientes. Conclusiones: Dos años de tratamiento con ADV7103 mejoraron el crecimiento y la DMO de columna. Estos resultados sugieren que el control de la acidosis con dicho tratamiento provoca una mejora de parámetros óseos. (AU)

A velocidade de infusão da solução poli-iônica intravenosa contendo 84mEq/L de lactato determina a intensidade do efeito alcalinizante em equinos / The intravenous polyionic solution with 84mEq/L of lactate infusion rate determines the intensity of the alkalizing effect in horses

O objetivo deste trabalho foi verificar os efeitos da solução poli-iônica intravenosa contendo 84mEq/L de lactato (L84) sobre os equilíbrios hidroeletrolítico e ácido-base de equinos, quando administrada de forma rápida ou lenta. Cinco equinos sadios adultos receberam a infusão contínua intravenosa da L84, em volume correspondente a 10% do peso corporal, em duas ocasiões: a) infusão rápida (16,66mL/kg/h) durante seis horas; b) infusão lenta (8,33mL/kg/h) durante 12 horas. Amostras de sangue venoso foram colhidas ao início da infusão (hora zero) e três, seis, nove, 12 e 24 horas após, e amostras de urina nas horas zero, seis, 12 e 24. Determinaram-se pH (sanguíneo e urinário), pCO2, HCO3 -, BE, PPT, lactato L, Na+, K+, Cl-, AG, SID, Atot, VVP, densidade urinária e excreções fracionadas urinárias de lactato L, Na+, K+ e Cl-. A L84 provoca efeito alcalinizante iatrogênico de menor magnitude quando administrada de forma lenta, porque os mecanismos renais, atuantes durante o período de infusão, promovem a correção gradativa do desequilíbrio. Pode-se concluir que a infusão de forma lenta da solução L84 em equinos é recomendável nos casos em que se suspeite de acidose metabólica e não seja possível quantificar o grau do desequilíbrio.(AU)

The aim of this study was to investigate the effects of an intravenous polyionic solution containing 84mEq/L of lactate (L84) on the hydroelectrolyte and acid-base balances when administered quickly or slowly in horses. Five healthy adult horses received the L84 solution, in a volume corresponding to 10% of BW, by continuous intravenous infusion, in two instants: a) rapid infusion (16.66mL/kg/h) during 6 hours; b) slow infusion (8.33mL/kg/h) during 12 hours. Venous blood samples were taken at the beginning of the infusion (hour 0) and 3, 6, 9, 12, and 24 hours after. Urine samples were taken at 0, 6, 12, and 24h. pH (blood and urine), pCO2, HCO3-, BE, TPP, L-lactate, Na+, K+, Cl-, AG, SID, Atot, PVV, urine specific gravity, and L-lactate, Na+, K+, and Cl- renal fractional clearance were determined. The L84 solution causes lower magnitude alkalizing effect when administered slowly, due to the gradual correction of the iatrogenic imbalance by the kidneys during the infusion period. The L84 solution infused at a low rate in horses could be recommended in cases where metabolic acidosis is suspected and it is not possible to quantify the imbalance degree.(AU)

Agua alcalinizante y con alto contenido de magnesio: los posibles efectos beneficiosos para la salud / Alkaline water and with high level of magnesium: possible benefits for health

Introducción: el consumo de dietas con un potencial alcalinizante ha sido asociado con varios efectos beneciosos sobre la salud. El potencial alcalinizante de un alimento en particular puede evaluarse mediante el cálculo del PRAL, una fórmula que tiene en cuenta el contenido de sulfato, fosfato, cloruro, sodio, calcio, potasio y magnesio de los alimentos. Objetivos: revisar la literatura para vericar el efecto del magnesio y alimentos/agua con potencial alcalinizante para la salud. También evaluar la capacidad de un filtro comercial para hacer el agua más alcalinizante y aumentar su contenido de magnesio. Materiales y métodos: se utilizaron cuatro filtros y el PRAL se calculó para todas las muestras; los valores se expresaron como media ± desviación estándar. Resultados: se encontró un aumento en el pH (IC 95%: 2,702 a -2,548; p<0,0001) y una reducción en el valor de PRAL (IC 95%: 1,418 a 2,081; p<0,0001). El magnesio fue el mayor predictor de un valor de PRAL alcalinizante dado que hubo un incremento estadísticamente significativo (IC 95%: 54,00 a -39,16; p<0,0001) en el contenido de magnesio después del proceso de filtración independiente de la fuente de agua. Conclusiones: la mayoría de los estudios sugiere que el consumo de alimentos alcalinizantes se asocia con una reducción de la resorción ósea y la inhibición de la actividad de los osteoclastos. El consumo de magnesio se relaciona con un menor riesgo de enfermedad cardiovascular, diabetes tipo II y determinados tipos de demencia como la enfermedad de Alzheimer.

Introduction: the intake of alkalizing potential diets has been associated with various bene¬cial effects on health. The alkalizing potential of a particular food can be evaluated by the PRAL calculation, a formula considering the content of sulfate, Phosphate, chloride, sodium, calcium, potassium and magnesium in food. Objectives: to check the scientific literature to verify the effect of magnesium and food/water with alkalizing potential for health. The capacity of a commercial filter to make water more alkalizing and increase the content of magnesium was also evaluated. Materials and methods: four filters were used and PRAL was calculated for all samples, and the values were reported as mean ± standard deviation. Results: an increase in pH was observed (CI 95%: -2,702 to -2,548; p<0,0001) and a reduction in the PRAL value (CI 95%: 1,418 to 2,081; p<0,0001). Magnesium was the major predictor of an alkalizing PRAL value, since there was a statistically significant increase (CI 95%: -54,00 to -39,16; p<0,0001) in the content of magnesium after the independent filtration process of water source. Conclusions: most of the studies suggest that the consumption of alkalizing water is associated with a reduction in bone resorption and inhibition of osteoclast activity. The consumption of magnesium is associated with a less risk of cardiovascular disease, type II diabetes and certain types of dementia such as Alzheimer.

Efeito alcalinizante de soluções eletrolíticas intravenosas com concentrações elevadas de lactato de sódio infundidas em bezerros sadios / Alkalinizing effect of intravenous electrolyte solutions with high sodium lactate concentrations infused in healthy calves

Com o objetivo de investigar o potencial alcalinizante de soluções eletrolíticas com concentrações elevadas de lactato de sódio em bezerros sadios, foram idealizadas seis soluções contendo 28, 56 e 84mEq/L de lactato (L28, L56 e L84) ou de bicarbonato (B28, B56 e B84), com concentrações de sódio, de potássio e de cálcio semelhantes às da solução de Ringer com lactato (SRL). As soluções contendo bicarbonato de sódio foram utilizadas como padrão para comparação. Seis bezerros receberam, por via intravenosa, todas as seis soluções, uma a cada vez, com intervalo de quatro a cinco dias entre as infusões, em volume correspondente a 10% do peso corporal, durante cinco horas (20mL/kg/h). Amostras de sangue venoso e de urina foram coletadas antes de iniciar a infusão, na metade do volume, ao término e duas horas e meia após o término da infusão. Determinaram-se concentração de proteína plasmática total, pH sanguíneo e urinário, pCO2, HCO3 -, BE, concentração plasmática e urinária de lactato L e concentrações séricas e urinárias de Na+, K+, Cl- e creatinina. A solução L28, idêntica à SRL, provocou discreto incremento da reserva alcalina e, consequentemente, produziu efeito alcalinizante insuficiente para a correção de estados de acidose metabólica. A solução L84, além de provar-se segura, provocou o maior aumento da reserva alcalina, equivalente à B84, e, assim, produziu efeito capaz de corrigir o grau moderado de acidose metabólica.

The alkalinizing effects of electrolyte solutions with high concentration of sodium lactate were evaluated in healthy calves. Six solutions were formulated containing 28, 56 and 84mEq/L of lactate (L28, L56 and L84) or bicarbonate (B28, B56 and B84), and sodium, potassium and calcium concentrations similar to the lactated Ringer's solution (LRS). The solutions containing sodium bicarbonate were used as a standard for comparison. Six calves received all six solutions intravenously, one at a time, with an interval of four to five days between the infusions, in a volume corresponding to 10% of body weight, during five hours (20mL/kg/h). Venous blood and urine samples were taken prior to the beginning of the infusion, at a half volume, at the end and two and a half hours after the end of the infusion. Total plasma protein concentration, urinary and blood pH, blood pCO2, HCO3 - and BE, plasma and urine L lactate concentration and serum and urine Na+, K+, Cl- and creatinine concentrations were measured. The L28 solution, equal to LRS, caused a slight increase in the alkaline reserve, producing an alkalinizing effect insufficient for correction of metabolic acidosis states. The L84 solution was safe and produced the greater increase in the alkaline reserve, equivalent to B84 solution, and suitable for correcting a moderate degree of metabolic acidosis.

Avaliação do potencial alcalinizante das águas minerais comercialmente disponíveis em território brasileiro / Alkalizing potential evaluation of commercially available mineral waters in Brazil

OBJECTIVE:To characterize the profile of commercially available mineral waters in Brazil (from national and international sources) by calculating the potential renal acid load (PRAL). METHODS: We evaluated 308 commercially available mineral waters in the five Brazilian macro regions. The content of sulfate, chloride, sodium, potassium, magnesium and calcium from mineral waters were obtained to calculate the PRAL, using Remers & Manz formula, adapted for mineral waters. RESULTS: From the 308 mineral waters collected, 256 were included in this analysis. We found a great variability in the composition of mineral waters according to the source and country of origin. All the components analyzed were present in greater quantities in the mineral waters from international sources and differed significantly from the values found in the mineral waters from Brazilian sources, with the exception of potassium and sodium (Mg: 1,9 vs 6,8, p=0,0008; Ca: 5,78 vs 32,9, p=0,001; SO4: 0,9 vs 13, p<0,0001; Cl: 1,49 vs 12, p=0,0019, mineral waters from Brazilian sources versus international sources, respectively). The PRAL value of mineral waters from Brazilian sources was also statistically different (-0,39 vs -1,39; p=0,0025). The potential basifying / acidifying effects of the mineral water evaluated by PRAL did not correlate with the pH value. The magnesium and bicarbonate content were the major predictors of a negative PRAL - the higher the content thereof, lower the PRAL. CONCLUSION: The mineral waters from Brazilian sources have a low grade of mineralization and the vast majority (n=201) have a PRAL value considered neutral

OBJETIVO: Caracterizar o perfil de águas minerais comercialmente disponíveis em território brasileiro (provenientes de fontes nacionais e internacionais) através do cálculo do potencial de carga ácida renal (PRAL). MÉTODOS: Foram avaliadas 308 águas minerais comercialmente disponíveis nas cinco macrorregiões brasileiras. O conteúdo de sulfato, cloreto, sódio, potássio, magnésio e cálcio das águas minerais foram obtidos para cálculo do PRAL, que foi realizado através da fórmula de Remer e Manz, adaptada para águas minerais. RESULTADOS: Das 308 águas minerais coletadas, foram incluídas 256 nesta análise. Foi encontrada uma grande variabilidade na composição das águas minerais de acordo com a fonte de extração e país de origem. Todos os componentes analisados apresentaram-se em maior quantidade nas águas minerais de fontes internacionais e diferiram significantemente dos valores encontrados nas águas minerais de fontes brasileiras, com exceção do potássio e sódio (Mg: 1,9 vs 6,8, p=0,0008; Ca: 5,78 vs 32,9, p=0,001; SO4: 0,9 vs 13, p<0,0001; Cl: 1,49 vs 12, p=0,0019, fontes brasileiras versus fontes internacionais, respectivamente). O valor de PRAL das águas minerais de fontes brasileiras também foi diferente (-0,39 vs -1,39; p=0,0025). O potencial alcalinizante/ acidificante das águas minerais avaliado pelo PRAL não esteve correlacionado com o valor de pH. O magnésio e bicarbonato apresentaram-se como os principais preditores negativos do PRAL ­ quanto maior o teor destes, menor o PRAL. CONCLUSÃO: As águas minerais de fontes brasileiras possuem baixo grau de mineralização e a maioria (n=201) com valor de PRAL considerado neutro

Efectos de la alcalosis metabólica inducida por la dieta en el rendimiento anaeróbico de alta intensidad / Effects of the metabolic alkalosis induced by the diet in the high intensity anaerobic performance

Objetivos: El propósito principal de este estudio es comparar el efecto de una alcalosis y acidosis inducidas por la dieta sobre el rendimiento en un esfuerzo anaeróbico láctico mantenido. Métodos: Para ello, trece sujetos activos se sometieron de forma cruzada a sendas dietas durante dos días y medio. Inmediatamente después realizaron una prueba de esfuerzo anaeróbica láctica máxima de estado estable hasta el agotamiento sobre cicloergómetro a 250W.Resultados: La valoración de las dietas mostró una diferencia significativa en la excreción renal neta de ácidos (NAE) estimada, así como un déficit calórico del54% en la dieta alcalinizante, debido principalmente a una ingesta reducida de hidratos de carbono. En un 83% de los sujetos aumentó el pH urinario tras la dieta alcalinizante. El 77% incrementó sus niveles de lactato en sangre en la prueba tras la dieta alcalina. Los tiempos hasta la extenuación durante la prueba mejoraron o se mantuvieron en un 58% de los sujetos, siendo las mujeres las que mejor respondieron a la dieta con un 83% de casos. Conclusiones: Parece haber evidencias de mejora de rendimiento en esfuerzos de tipo anaeróbico láctico hasta el agotamiento de 60 s a 2 min de duración tras consumir una dieta con potencial alcalinizante (AU)

Objectives: The purpose of this study is to compare the effects of two diets, one acidifier and the other alkalizer, on the sport performance in an extreme anaerobic stress test. Methods: For that purpose thirteen individuals were subjected to two such diets in a crossed test for two and a half days. Immediately after, they were tested in a maximumlactic anaerobic stress test of stable state to exhaustion on an ergo-cycle at 250W. Results: The assessment of the diets yielded a significant difference in the estimated NAE (net acid excretion) and a caloric deficit of 54% on the alkalizer diet,mainly due to a reduced ingestion of carbohydrates.The urinary pH increased by 83% for the individuals subjected to the alkalizer diet, 77% of those subjects experienced an increase in their blood lactate level during the test. The time to exhaustion while on the test improved or remained in 58% of the subjects, being the females who reacted best to the diet in 83% of the cases. Conclusions: There seems to be evidence of improvement in extreme anaerobic stress test to exhaustion from 60s to 2 mins of duration after consuming a diet with alkalizer potential (AU)

Shock séptico con distrés respiratorio del adulto y Alcaligenes xylosoxidans / Septic shock with adult respiratory distress syndrome and Alcaligenes xylosoxidans

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Peritonitis bacteriana espontánea por Alcaligenes xylosoxidans / Spontaneous bacterial peritonitis caused by Alcaligenes xylosoxidans

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Estudio comparativo del fenotipo HLA DR en niños aragoneses con enfermedad celíaca y población control de la misma región / Comparative study of HLA DR phenotype in children from Aragón (Spain) with celiac disease and control population within the same geographical area

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