Regulation of kidney on potassium balance and its clinical significance / 生理学报

Virtually all of the dietary potassium intake is absorbed in the intestine, over 90% of which is excreted by the kidneys regarded as the most important organ of potassium excretion in the body. The renal excretion of potassium results primarily from the secretion of potassium by the principal cells in the aldosterone-sensitive distal nephron (ASDN), which is coupled to the reabsorption of Na+ by the epithelial Na+ channel (ENaC) located at the apical membrane of principal cells. When Na+ is transferred from the lumen into the cell by ENaC, the negativity in the lumen is relatively increased. K+ efflux, H+ efflux, and Cl- influx are the 3 pathways that respond to Na+ influx, that is, all these 3 pathways are coupled to Na+ influx. In general, Na+ influx is equal to the sum of K+ efflux, H+ efflux, and Cl- influx. Therefore, any alteration in Na+ influx, H+ efflux, or Cl- influx can affect K+ efflux, thereby affecting the renal K+ excretion. Firstly, Na+ influx is affected by the expression level of ENaC, which is mainly regulated by the aldosterone-mineralocorticoid receptor (MR) pathway. ENaC gain-of-function mutations (Liddle syndrome, also known as pseudohyperaldosteronism), MR gain-of-function mutations (Geller syndrome), increased aldosterone levels (primary/secondary hyperaldosteronism), and increased cortisol (Cushing syndrome) or deoxycorticosterone (hypercortisolism) which also activate MR, can lead to up-regulation of ENaC expression, and increased Na+ reabsorption, K+ excretion, as well as H+ excretion, clinically manifested as hypertension, hypokalemia and alkalosis. Conversely, ENaC inactivating mutations (pseudohypoaldosteronism type 1b), MR inactivating mutations (pseudohypoaldosteronism type 1a), or decreased aldosterone levels (hypoaldosteronism) can cause decreased reabsorption of Na+ and decreased excretion of both K+ and H+, clinically manifested as hypotension, hyperkalemia, and acidosis. The ENaC inhibitors amiloride and Triamterene can cause manifestations resembling pseudohypoaldosteronism type 1b; MR antagonist spironolactone causes manifestations similar to pseudohypoaldosteronism type 1a. Secondly, Na+ influx is regulated by the distal delivery of water and sodium. Therefore, when loss-of-function mutations in Na+-K+-2Cl- cotransporter (NKCC) expressed in the thick ascending limb of the loop and in Na+-Cl- cotransporter (NCC) expressed in the distal convoluted tubule (Bartter syndrome and Gitelman syndrome, respectively) occur, the distal delivery of water and sodium increases, followed by an increase in the reabsorption of Na+ by ENaC at the collecting duct, as well as increased excretion of K+ and H+, clinically manifested as hypokalemia and alkalosis. Loop diuretics acting as NKCC inhibitors and thiazide diuretics acting as NCC inhibitors can cause manifestations resembling Bartter syndrome and Gitelman syndrome, respectively. Conversely, when the distal delivery of water and sodium is reduced (e.g., Gordon syndrome, also known as pseudohypoaldosteronism type 2), it is manifested as hypertension, hyperkalemia, and acidosis. Finally, when the distal delivery of non-chloride anions increases (e.g., proximal renal tubular acidosis and congenital chloride-losing diarrhea), the influx of Cl- in the collecting duct decreases; or when the excretion of hydrogen ions by collecting duct intercalated cells is impaired (e.g., distal renal tubular acidosis), the efflux of H+ decreases. Both above conditions can lead to increased K+ secretion and hypokalemia. In this review, we focus on the regulatory mechanisms of renal potassium excretion and the corresponding diseases arising from dysregulation.

Expression changes of NaV channel subunits correlate with developmental maturation of electrophysiological characteristics of rat cerebellar Purkinje neurons / 南方医科大学学报

OBJECTIVE@#To investigate the variations in the expression of voltage-gated sodium (Nav) channel subunits during development of rat cerebellar Purkinje neurons and their correlation with maturation of electrophysiological characteristics of the neurons.@*METHODS@#We observed the changes in the expression levels of NaV1.1, 1.2, 1.3 and 1.6 during the development of Purkinje neurons using immunohistochemistry in neonatal (5-7 days after birth), juvenile (12-14 days), adolescent (21-24 days), and adult (42-60 days) SD rats. Using whole-cell patch-clamp technique, we recorded the spontaneous electrical activity of the neurons in ex vivo brain slices of rats of different ages to analyze the changes of electrophysiological characteristics of these neurons during development.@*RESULTS@#The expression of NaV subunits in rat cerebellar Purkinje neurons showed significant variations during development. NaV1.1 subunit was highly expressed throughout the developmental stages and increased progressively with age (P < 0.05). NaV1.2 expression was not detected in the neurons in any of the developmental stages (P > 0.05). The expression level of NaV1.3 decreased with development and became undetectable after adolescence (P < 0.05). NaV1.6 expression was not detected during infancy, but increased with further development (P < 0.05). NaV1.1 and NaV1.3 were mainly expressed in the early stages of development. With the maturation of the rats, NaV1.3 expression disappeared and NaV1.6 expression increased in the neurons. NaV1.1 and NaV1.6 were mainly expressed after adolescence. The total NaV protein level increased gradually with development (P < 0.05) and tended to stabilize after adolescence. The spontaneous frequency and excitability of the Purkinje neurons increased gradually with development and reached the mature levels in adolescence. The developmental expression of NaV subunits was positively correlated with discharge frequency (r=0.9942, P < 0.05) and negatively correlated with the excitatory threshold of the neurons (r=0.9891, P < 0.05).@*CONCLUSION@#The changes in the expression levels of NaV subunits are correlated with the maturation of high frequency electrophysiological properties of the neurons, suggesting thatmature NaV subunit expressions is the basis of maturation of electrophysiological characteristics of the neurons.

Los inhibidores SGLT2: una mirada al futuro del tratamiento de la insuficiencia cardiaca / Sodium-glucose cotransporter 2 inhibitors for the management of heart failure

Heart failure (HF) is a global health problem. There is a strong association h between HF and type 2 diabetes mellitus (DM2), with an increasing prevalence of patients having both conditions concomitantly. Sodium-glucose cotransporter 2 inhibitors (ISGLT2) significantly reduce cardiovascular events, including cardiovascular death. In this article we will focus on the current evidence about the effectiveness of these medications in adults with heart failure with reduced or preserved ejection fraction.

Functional roles of sodium-calcium exchange in autorhythmicity and action potential of murine fetal cardiomyocytes at early developmental stage / 生理学报

The aim of the present paper was to study the role of sodium calcium exchanger (NCX) in the generation of action potentials (APs) in cardiomyocytes during early developmental stage (EDS). The precisely dated embryonic hearts of C57 mice were dissected and enzymatically dissociated to single cells. The changes of APs were recorded by whole-cell patch-clamp technique before and after administration of NCX specific blockers KB-R7943 (5 μmol/L) and SEA0400 (1 μmol/L). The results showed that, both KB-R7943 and SEA0400 had potent negative chronotropic effects on APs of pacemaker-like cells, while such effects were only observed in some ventricular-like cardiomyocytes. The negative chronotropic effect of KB-R7943 on ventricular-like cardiomyocytes was accompanied by shortening of AP duration (APD), whereas such an effect of SEA0400 was paralleled by decrease in velocity of diastolic depolarization (Vdd). From embryonic day 9.5 (E9.5) to E10.5, the negative chronotropic effects of KB-R7943 and SEA0400 on ventricular-like APs of embryonic cardiomyocytes gradually disappeared. These results suggest that, in the short-term development of early embryo, the function of NCX may experience developmental changes as evidenced by different roles of NCX in autorhythmicity and APs generation, indicating that NCX function varies with different conditions of cardiomyocytes.

Fluid and hemodynamic management in hemodialysis patients: challenges and opportunities / Manejo hídrico e hemodinâmico em pacientes em hemodiálise: desafios e oportunidades

Abstract Fluid volume and hemodynamic management in hemodialysis patients is an essential component of dialysis adequacy. Restoring salt and water homeostasis in hemodialysis patients has been a permanent quest by nephrologists summarized by the 'dry weight' probing approach. Although this clinical approach has been associated with benefits on cardiovascular outcome, it is now challenged by recent studies showing that intensity or aggressiveness to remove fluid during intermittent dialysis is associated with cardiovascular stress and potential organ damage. A more precise approach is required to improve cardiovascular outcome in this high-risk population. Fluid status assessment and monitoring rely on four components: clinical assessment, non-invasive instrumental tools (e.g., US, bioimpedance, blood volume monitoring), cardiac biomarkers (e.g. natriuretic peptides), and algorithm and sodium modeling to estimate mass transfer. Optimal management of fluid and sodium imbalance in dialysis patients consist in adjusting salt and fluid removal by dialysis (ultrafiltration, dialysate sodium) and by restricting salt intake and fluid gain between dialysis sessions. Modern technology using biosensors and feedback control tools embarked on dialysis machine, with sophisticated analytics will provide direct handling of sodium and water in a more precise and personalized way. It is envisaged in the near future that these tools will support physician decision making with high potential of improving cardiovascular outcome.

Resumo O volume de fluidos e o controle hemodinâmico em pacientes em hemodiálise é um componente essencial da adequação da diálise. A restauração da homeostase do sal e da água em pacientes em hemodiálise tem sido uma busca constante por parte dos nefrologistas, no que condiz à abordagem do "peso seco. Embora essa abordagem clínica tenha sido associada a benefícios no desfecho cardiovascular, recentemente tem sido questionada por estudos que mostram que a intensidade ou agressividade para remover fluidos durante a diálise intermitente está associada a estresse cardiovascular e dano potencial a órgãos.para remover fluidos durante a diálise intermitente está associada a estresse cardiovascular e dano potencial a órgãos. Uma abordagem mais precisa é necessária para melhorar o desfecho cardiovascular nessa população de alto risco. A avaliação e monitorização do estado hídrico baseiam-se em quatro componentes: avaliação clínica, ferramentas instrumentais não invasivas (por exemplo, US, bioimpedância, monitorização do volume sanguíneo), biomarcadores cardíacos (e.g. peptídeos natriuréticos), algoritmos e modelagem de sódio para estimar a transferência de massa. O manejo otimizado do desequilíbrio hídrico e de sódio em pacientes dialíticos consiste em ajustar a remoção de sal e líquido por diálise (ultrafiltração, dialisato de sódio), e restringir a ingestão de sal e o ganho de líquido entre as sessões de diálise. Tecnologia moderna que utiliza biosensores e ferramentas de controle de feedback, hoje parte da máquina de diálise, com análises sofisticadas, proporcionam o manejo direto sobre o sódio e a água de uma maneira mais precisa e personalizada. Prevê-se no futuro próximo que essas ferramentas poderão auxiliar na tomada de decisão do médico, com alto potencial para melhorar o resultado cardiovascular.

Chloride and sodium ion concentrations in saliva and sweat as a method to diagnose cystic fibrosis / Dosagem da concentração dos íons cloreto e sódio na saliva e no suor para o reconhecimento de pacientes com fibrose cística

Abstract Objective: Cystic fibrosis diagnosis is dependent on the chloride ion concentration in the sweat test (≥ 60 mEq/mL - recognized as the gold standard indicator for cystic fibrosis diagnosis). Moreover, the salivary glands express the CFTR protein in the same manner as sweat glands. Given this context, the objective was to verify the correlation of saliva chloride concentration and sweat chloride concentration, and between saliva sodium concentration and sweat sodium concentration, in patients with cystic fibrosis and healthy control subjects, as a tool for cystic fibrosis diagnosis. Methods: There were 160 subjects enrolled: 57/160 (35.70%) patients with cystic fibrosis and two known CFTR mutations and 103/160 (64.40%) healthy controls subjects. Saliva ion concentration was analyzed by ABL 835 Radiometer® equipment and, sweat chloride concentration and sweat sodium concentration, respectively, by manual titration using the mercurimetric procedure of Schales & Schales and flame photometry. Statistical analysis was performed by the chi-squared test, the Mann -Whitney test, and Spearman's correlation. Alpha = 0.05. Results: Patients with cystic fibrosis showed higher values of sweat chloride concentration, sweat sodium concentration, saliva chloride concentration, and saliva sodium concentration than healthy controls subjects (p-value < 0.001). The correlation between saliva chloride concentration and sweat chloride concentration showed a positive Spearman's Rho (correlation coefficient) = 0.475 (95% CI = 0.346 to 0.587). Also, the correlation between saliva sodium concentration and sweat sodium concentration showed a positive Spearman's Rho = 0.306 (95% CI = 0.158 to 0.440). Conclusions: Saliva chloride concentration and saliva sodium concentration are candidates to be used in cystic fibrosis diagnosis, mainly in cases where it is difficult to achieve the correct sweat amount, and/or CFTR mutation screening is difficult, and/or reference methods for sweat test are unavailable to implement or are not easily accessible by the general population.

Resumo Objetivo: O diagnóstico da fibrose cística depende do valor da concentração de íons de cloreto no teste do suor (≥ 60 mEq/mL - reconhecido como o indicador-padrão para o diagnóstico da doença). Além disso, as glândulas salivares expressam a proteína RTFC igualmente às glândulas sudoríparas. Nesse contexto, nosso objetivo foi verificar a correlação da concentração de cloreto na saliva e a concentração de cloreto no suor e entre a concentração de sódio na saliva e a concentração de sódio no suor em pacientes com fibrose cística e indivíduos controles saudáveis, como uma ferramenta para diagnóstico de fibrose cística. Métodos: Contamos com a participação de 160 indivíduos [57/160 (35,70%) com fibrose cística e duas mutações no gene RTFC conhecidas e 103/160 (64,40%) indivíduos controles saudáveis]. A concentração de íons na saliva foi analisada pelo equipamento ABL 835 da Radiometer® e a concentração de cloreto no suor e sódio no suor, respectivamente, por titulação manual utilizando o método mercurimétrico de Schales & Schales e fotometria de chama. A análise estatística foi realizada pelo teste qui-quadrado, pelo teste de Mann-Whitney e pela correlação de Spearman. Alpha = 0,05. Resultados: Os pacientes com fibrose cística apresentaram maiores valores na concentração de cloreto no suor, concentração de sódio no suor, concentração de cloreto na saliva e concentração de sódio na saliva do que os indivíduos-controle saudáveis (valor de p < 0,001). A correlação entre as concentrações de cloreto na saliva e cloreto no suor mostrou Rho de Spearman (coeficiente de correlação) positivo = 0,475 (IC de 95% = 0,346 a 0,587). Além disso, a correlação entre concentração de sódio na saliva e concentração de sódio no suor mostrou Rho de Spearman positivo = 0,306 (IC de 95% = 0,158 a 0,440). Conclusões: A concentração de cloreto na saliva e a concentração de sódio na saliva são candidatas a ser usadas como diagnóstico de fibrose cística, principalmente em casos em que é difícil atingir a quantidade correta de suor, e/ou o exame da mutação RTFC é difícil e/ou o método de referência para o teste do suor não se encontra disponível ou não é de fácil acesso ao público em geral.

Valores de referencia de oxalato, calcio, citrato, ácido úrico, fósforo, magnesio, sulfato y sodio urinarios en alumnos de la carrera de bioquímica de la Universidad Nacional del Litoral, Argentina / Reference values for urinary oxalate, calcium, citrate, uric acid, phosphate, magnesium, sulphate and sodium in biochemistry students at Universidad Nacional del Litoral, Argentina

INTRODUCCIÓN: La urolitiasis (UL) es una alteración frecuente, cuya incidencia ha aumentado en el último cuarto del siglo XX. Para su diagnóstico se realizan estudios metabólicos para lo cual es necesario contar con valores de referencia (VR) establecidos para la población en cuestión. OBJETIVO: El objetivo del trabajo fue determinar VR de calcio, oxalato, citrato, úrico, fósforo, magnesio, sulfato y sodio en orina de 24 horas de alumnos de la Facultad de Bioquímica y Ciencias Biológicas de la Universidad Nacional del Litoral, Santa Fe, Argentina. Con los VR hallados se determinó la frecuencia de alteraciones y se la comparó con datos bibliográficos. MATERIAL Y MÉTODOS: Se utilizó la guía NCCLSC28-A3, 2008. La muestra de referencia fue de 69 alumnos. Se utilizaron métodos enzimáticos-colorimétricos, espectrofotómetro Metrolab 1600 plus, electrodos ion selectivo DIESTRO. RESULTADOS: Los VR hallados (IC 95%) fueron para el oxalato: 1,96-45,08; calcio: 20,65-250,74; citrato: 112,78-666,01; ácido úrico 58,73-782,17; fósforo 238,37-1051,44; magnesio 28,7-146,67 todos en mg/24h; sulfato 3,15-25,18 mmol/24h y sodio 42,81-285,3 mEq/24h. Se encontró un 3% hiperoxaluria, 12% hipercalciuria, 3% hipocitraturia y 6% hiperuricosuria, 6% hiperfosfaturia, 6% hipomagnesuria, 7% hipernatriuria, 0% hipersulfaturia. Los VR comparados mostraron coincidencias para algunos analitos y para otros amplias diferencias. CONCLUSIONES: El diagnóstico de la alteración metabólica para el estudio de UL varía según el valor de referencia utilizado. Adoptar valores establecidos para otras poblaciones, incluidos los de los fabricantes de los kits comerciales, conducen a un diagnóstico que puede no ser acorde a la situación clínica del paciente

INTRODUCTION: Urolithiasis (UL) is a common disease whose incidence increased in the last quarter of the twentieth century. Metabolic evaluation is necessary for diagnosis, which requires the establishment of reference values (RV) for the population in question. OBJECTIVE: To determine the RV for calcium, oxalate, citrate, uric acid, phosphate, magnesium, sulphate and sodium in 24-hour urine belonging to students from the School of Biochemistry and Biological Sciences at Universidad Nacional del Litoral, province of Santa Fe, Argentina. Once RV were established, a frequency of alterations was determined and then compared with literature data. METHODS: The NCCLSC28-A3 guideline (2008) was used. The study group included 69 students. The enzymatic colorimetric method, a Metrolab 1600 plus spectrophotometer and a DIESTRO ion-selective electrode were also employed. Results: The RV found (95 % CI) were the following: oxalate, 1.96-45.08; calcium, 20.65-250.74; citrate, 112.78-666.01; uric acid, 58.73-782.17; phosphate, 238.37-1051.44; magnesium, 28.7-146.67, all these values expressed as mg/24h; sulphate, 3.15-25.18 mmol/24h, and sodium, 42.81-285.3 mEq/24h. These findings emerged as well: hyperoxaluria, 3%; hypercalciuria 12%; hypocitraturia, 3%; hyperuricosuria, 6%; hyperphosphaturia, 6%; hypomagnesuria, 6%; hypernatriuria, 7%, and hypersulphaturia, 0%. When RV were compared, some analyte levels were similar and others showed a considerable difference. CONCLUSIONS: The diagnosis of UL through the study of metabolic changes is different according to the reference value used. Applying reference values established for other populations, including those of commercial kits manufacturers, may lead to a diagnosis which does not match the clinical condition of the patient

Possible senescence associated change in the predominant &alpha -Na+/K+ ATP-ase isoform in the renal cortex of the rat

With aging the kidney exhibits progressive deterioration, with a decrease in renal function. Most of the filtered Na+ is actively reabsorbed in the proximal tubules through different transporters located in apical membrane. This process is possible because basolateral Na+/K+-ATP-ase generates electrochemical conditions necessary for energetically favorable Na+ transport. The α-subunit is the catalytic domain of Na+/K+-ATP-ase. There are three isoforms of the α/subunit present in rat kidney. The present study was undertaken to examine the expression pattern of rat α-Na+/K+-ATP-ase during senescence. We tested the impact of aging on mRNA expression of α-Na+/K+-ATP-ase in cortex and medulla of aged Wistar rats. We observed a significant expression decrease in mRNA levels and a possible change of isoform in the cortex of aged animals. These expression changes observed for αsubunit could be contributing to affect the renal function in conditions of water and salt stress.

Con el avance de la edad los riñones exhiben un deterioro funcional progresivo con disminución de la función renal. La mayor parte del sodio (Na+) filtrado es reabsorbido activamente en los túbulos proximales a través de diferentes transportadores ubicados en la membrana apical. Este proceso es posible por la existencia de la Na+/K+-ATP-asa basolateral, que genera las condiciones electroquímicas necesarias para que el transporte de Na+ sea energéticamente favorable. La subunidad αde la Na+/K+-ATP-asa es el dominio catalítico de la enzima. Existen tres isoformas de subunidad α, que están presentes en el riñón de la rata. En este trabajo se examinan los patrones de expresión de la α-Na+/K+-ATP-asa durante la senescencia. Se estudió así si el aumento de la edad incidía en la expresión del ARNm de la α-Na+/K+-ATP-asa en corteza y médula renal de ratas Wistar senescentes. Se observó una disminución en la expresión del ARNm de la subunidad αy un posible cambio de isoforma predominante en la corteza de los animales senescentes. Los cambios observados para la expresión de la subunidad αpodrían contribuir a afectar la función renal en condiciones de estrés hídrico y salino.

Factores asociados a hiponatremia adquirida en la comunidad / Factors associated with community-acquired hyponatremia

El desarrollo de la hiponatremia en la comunidad es un aspecto poco estudiado, y su frecuencia y los factoresque la condicionan son poco conocidos. Objetivos: Estudiar los factores clínicos y de laboratorio asociados a la hiponatremia de pacientes incidentes en el servicio de emergencia de un hospital general. Material y métodos: Estudio de casos y controles. Los casos fueron pacientes con Na+ sérico5 mg/dl. Se contrastaron las variables edad, sexo, sistemas comprometidos, gravedad del paciente y valor de loselectrolitos; gases arteriales; urea y creatinina. El tamaño de muestra fue de 20 casos y 40 controles (confianza 95%, potencia 80% y OR 4)...

The prevalence and associated factors for developing hyponatremia in the community have not been adequately studied. Objectives: To study the clinical and laboratory factors associated with hyponatremia in patients attending the emergency room of a general hospital. Methods: A case-control was carried out, cases were patients with serum sodium values below 135 mEq/l at the time of admission to the emergency room of Hospital Cayetano Heredia and controls were patients admitted at the same time as cases with serum sodium values from 135 y 145 mEq/l. Patients with serum creatinine values >5 mg/dl were excluded...

The effect of NaCl 0.9% and NaCl 0.45% on sodium, chloride, and acid-base balance in a PICU population / Efeito do NaCl a 0,9% e do NaCl a 0,45% sobre o sódio, cloreto e equilíbrio ácido-base em uma população de UTIP

ABSTRACT OBJECTIVES: To study the effect of two intravenous maintenance fluids on plasma sodium (Na), and acid-base balance in pediatric intensive care patients during the first 24 h of hospitalization. METHODS: A prospective randomized controlled study was performed, which allocated 233 patients to groups: (A) NaCl 0.9% or (B) NaCl 0.45%. Patients were aged 1 day to 18 years, had normal electrolyte concentrations, and suffered an acute insult (medical/surgical). Main outcome measured: change in plasma sodium. Parametric tests: t-tests, ANOVA, X 2 statistical significance level was set at a = 0.05. RESULTS: Group A (n = 130): serum Na increased by 2.91 (±3.9) mmol/L at 24 h (p < 0.01); 2% patients had Na higher than 150 mmol/L. Mean urinary Na: 106.6 (±56.8) mmol/L. No change in pH at 0 and 24 h. Group B (n = 103): serum Na did not display statistically significant changes. Fifteen percent of the patients had Na < 135 mmol/L at 24 h. The two fluids had different effects on respiratory and post-operative situations. CONCLUSIONS: The use of saline 0.9% was associated with a lower incidence of electrolyte disturbances.

RESUMO OBJETIVO: Estudar o efeito de dois fluidos de manutenção intravenosos sobre o sódio (Na) plasmático e o equilíbrio ácido-base em pacientes de terapia intensiva pediátrica durante as primeiras 24 horas de internação. MÉTODOS: Foi feito um estudo controlado randomizado prospectivo. Alocamos aleatoriamente 233 pacientes para os grupos: (A) NaCl a 0,9% e (B) NaCl a 0,45%. Os pacientes com um dia a 18 anos apresentavam concentrações normais de eletrólitos e sofriam de insulto agudo (médico/cirúrgico). Principal resultado: variação no sódio plasmático. Testes paramétricos: teste t, Anova, qui-quadrado. O nível de relevância estatística foi estabelecido em a = 0,05. RESULTADOS: Grupo A (n = 130): o Na sérico aumentou 2,91 (± 3,9) mmol L-1 em 24 h (p < 0,01); 2% dos pacientes apresentaram Na acima de 150 mmol L-1. Concentração média de Na na urina: 106,6 (± 56,8) mmol L-1. Sem alteração no pH em 0 e 24 horas. Grupo B (n = 103): o Na sérico não apresentou alterações estatisticamente significativas; 15% dos pacientes apresentaram Na < 135 mmol L-1 em 24 h. Os dois fluidos tiveram efeitos diferentes sobre as situações respiratória e pós-operatória. CONCLUSÃO: O uso de solução fisiológica a 0,9% foi associado à menor incidência de distúrbios eletrolíticos.

Anatomopathology of the Superstructure of the Stapes in Patients with Otosclerosis

Introduction Otosclerosis is a disease that causes bone resorption and deposition in the auditory structures, leading to deafness. Many studies have evaluated the histopathology of the stapes footplate in this disease (osteoblasts, osteoclasts, vascular proliferation, fibroblasts, and histiocytes), but we found no studies in the literature involving the histology of the superstructure of the stapes. Objectives To perform an analysis under optical microscopy of histopathologic findings of the superstructure of the stapes from patients with otosclerosis. Methods A contemporary cross-sectional cohort study of pathology analysis of superstructures of the stapes of patients with otosclerosis. Results Fifteen superstructures of stapes in patients with otosclerosis operated in our service and four stapes of cadavers used for dissection (controls) were evaluated. No areas of bone resorption or deposition or presence of osteoclasts and osteoblasts in the superstructure of the stapes were found. However, we found in themore distal portions of the crura areas with prominent cementitious lines and woven bone, which was different than the mature trabecular bone found in the head of the stapes or in the controls. Conclusion There were histologic changes in the superstructure of the stapes in patients with otosclerosis operated in our service. .

In vitro response of date palm (Phoenix dactylifera L) to K/Na ratio under saline conditions

BACKGROUND: Salinity is a serious factor limiting the productivity of agricultural plants. One of the potential problems for plants growing under saline conditions is the inability to up take enough K+. The addition of K+ may considerably improve the salt tolerance of plants grown under salinity. It is assumed that increasing the K+ supply at the root zone can ameliorate the reduction in growth imposed by high salinity. The present study aims to determine whether an increase in the K/Na ratio in the external media would enhance the growth of date palm seedlings under in vitro saline conditions. METHODS: Date palm plants were grown at four concentrations of Na + K/Cl (mol/m³) with three different K/Na ratios. The 12 salt treatments were added to modified MS medium. The modified MS medium was further supplemented with sucrose at 30 g/l. RESULTS: Growth decreased substantially with increasing salinity. Growth expressed as shoot and root weight, enhanced significantly with certain K/Na ratios, and higher weight was maintained in the presence of equal K and Na. It is the leaf length, leaf thickness and root thickness that had significant contribution on total dry weight. Na+ contents in leaf and root increased significantly increased with increasing salinity but substantial decreases in Na+ contents were observed in the leaf and root with certain K/Na ratios. This could be attributed to the presence of a high K+ concentration in the media. The internal Na+ concentration was higher in the roots in all treatments, which might indicate a mechanism excluding Na+ from the leaves and its retention in the roots. K/Na ratios up to one significantly increased the leaf and root K+ concentration, and it was most pronounced in leaves. The K+ contents in leaf and root was not proportional to the K+ increase in the media, showing a high affinity for K+ uptake at lower external K+ concentrations, but this mechanism continues to operate even with high external Na+ concentrations. CONCLUSION: Increasing K/Na ratios in the growing media of date plam significantly reduced the absorption of Na+ less than 200 mM and also balance ions compartmentalization.

Incorporation of Na+/H+ antiporter gene from Aeluropus littoralis confers salt tolerance in soybean (Glycine max L.).

To develop a salt-tolerant soybean (Glycine max L.) cultivar, a minimal linear Na+/H+ antiporter gene cassette (35S CaMV promoter, open-reading-frame of AlNHX1 from Aeluropus littoralis and NOS terminator) was successfully expressed in soybean cultivar TF-29. Southern and Northern blot analysis showed that AlNHX1 was successfully incorporated into the genome and expressed in the transgenic plants. The AlNHX1 transgenic plant lines exhibited improved growth in severe saline condition (150 mM NaCl). The transgenic lines accumulated a lower level of Na+ and a higher level of K+ in the leaves than wild-type plants under saline condition (150 mM NaCl). Observations on the chlorophyll content, photosynthetic rates, malondialdehyde and relative electrical conductivity indicated that transgenic plants exhibited tolerance to salt stress, growing normally at salt concentrations up to 150 mM. These results demonstrated that AlNHX1 was successfully transferred into soybean and the salt-tolerance was improved by the overexpression of AlNHX1.

Roles of estrogen and progesterone in modulating renal nerve function in the rat kidney

The maintenance of extracellular Na+ and Cl- concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na+ and Cl- reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX) rats received 17β-estradiol benzoate (OVE, 2.0 mg·kg-1·day-1, sc) and progesterone (OVP, 1.7 mg·kg-1·day-1, sc). We assessed Na+ and Cl- fractional excretion (FENa+ and FECl- , respectively) and renal and plasma catecholamine release concentrations. FENa+ , FECl- , water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17β-estradiol benzoate but not by progesterone. Renal denervation did not alter FENa+ , FECl- , water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6±36.1 ng/g) and denervated rat groups (D: 102.1±15.7; ODE: 108.7±23.2; ODP: 101.1±22.1 ng/g). Furthermore, combining OVX + D (OD: 111.9±25.4) decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen, and progesterone in the modulation of renal function.

Predicting 24-hour urinary sodium excretion in Afro-Caribbean Barbadians by comparing urine sodium excretion over different durations versus spot collection / Predicción de la excreción del sodio urinario de 24 horas en Barbadenses Afrocaribeños mediante la comparación de la excreción del sodio en la orina en diferentes periodos de tiempo en contraste con la eecogida al azar

AIM: Urinary sodium excretion is used as an assessment tool for salt intake and salt handling. Even though cumbersome, the most reliable and readily used method in clinical and epidemiological studies is the 24-hour urine collection. This study investigates other appropriate means of predicting 24-hour urinary sodium excretion in a sample of Afro-Caribbeans in Barbados by assessing the correlation of actual and estimated urinary sodium excretion between a 24-hour urine collection sample, 12-hour (AM and PM), and spot (AM and PM) urine collections. METHOD: A convenient sample of 30 healthy participants of Afro-Caribbean origin between the ages of 21 and 55 years was recruited for the study. The 24-hour urine samples and anthropometric data were collected as documented in the study's standard clinical procedure. A 24-hour urine sample was collected as two separate 12-hour AM and PM samples. In addition, two spot samples (AM and PM) were taken during each 12-hour sample collection period. Analysis of the urinary sodium and creatinine was done with a Roche/Hitachi Modular System (Roche Diagnostics, IN, USA). SPSS version 19 was used to analyse the data to make inferences. RESULTS: Thirty Afro-Caribbean subjects participated in this study: 16 females and 14 males. The average age and body mass index (BMI) were 38 ± 17 years and 25.32 ± 5.98 kg/m2, respectively. The greatest correlation of the estimated 24-hour sodium excretion to the measured 24-hour sodium excretion was observed in the 12-hour PM sample (Pearson's correlation, r = 0.786, p < 0.001) followed by the 12-hour AM sample (Pearson's correlation, r = 0.774, p < 0.001). The PM spot sample showed a weaker, but still statistically significant correlation to the 24-hour timed sample (Pearson's correlation, r = 0.404, p < 0.045). The AM spot sample showed a very weak and insignificant correlation (Pearson's correlation, r = 0.05, p = 0.807) to the 24-hour timed sample. Similarly to the whole sample, the gender analysis demonstrated that estimated 24-hour sodium excretion in the female's 12-hour PM sample had the greatest correlation (r = 0.819, p < 0.001) to the measured 24- hour sodium excretion, followed by the 12-hour AM (r = 0.793, p = 0.001) and the PM spot samples (r = 0.741, p = 0.02). The correlation between variables is weaker in males compared to the females. CONCLUSION: Overall, this study shows a clear correlation between the estimated 24-hour sodium excretion from the 12-hour timed PM sample and the measured 24-hour sodium excretion. Such findings support the thought of using other alternatives to determine sodium excretion, in view of replacing the cumbersome 24-hour urinary collection with a smaller timed sample. Nonetheless, a more robust and randomized population sample as well as a method to correct for high creatinine variability is required to further enhance the significance of the obtained results.

OBJETIVO: La excreción del sodio en orina se utiliza como una herramienta de evaluación para la ingesta y manejo de la sal. Si bien resulta engorroso, el método más fiable y fácilmente utilizado en los estudios clínicos y epidemiológicos es la recolección de orina de 24 horas. Este estudio investiga otros medios apropiados de predicción de la excreción del sodio urinario de 24 horas en los afrocaribeños en Barbados, evaluando la correlación real y estimada de la excreción del sodio en orina entre una muestra de orina de 24 horas, 12 horas (AM y PM), y recogidas aleatorias (AM y PM). MÉTODO: Una muestra conveniente de 30 participantes sanos de origen afrocaribeño entre las edades de 21 y 55 años, fue reclutada para el estudio. Las muestras de orina de 24 horas y los datos antropométricos, fueron recogidos tal como se documenta en el procedimiento clínico estándar del estudio. Una muestra de orina de 24 horas fue recogida en forma de muestras de 12 horas AM y PM por separado. Además, se tomaron dos muestras (AM y PM) al azar durante cada periodo de recolección de muestras de 12 horas. El análisis del sodio y la creatinina urinarios fue hecho con un Sistema Modular Roche/Hitachi (Roche Diagnostic, IN, USA). La versión 19 de SPSS fue utilizada para analizar los datos para hacer las inferencias. RESULTADOS: Treinta sujetos afrocaribeños participaron en este estudio: 16 mujeres y 14 hombres. La edad media y el índice de masa corporal (IMC) promedio fueron 38 ± 17 años y 25.32 ± 5.98 kg/m², respectivamente. La mayor correlación de la excreción estimada de sodio de 24 horas con la excreción medida de sodio 24 horas, se observó en la muestra de 12 horas PM (correlación de Pearson, r = 0.786, p < 0.001), seguida por la muestra de 12 horas AM (correlación de Pearson, r = 0.774, p < 0.001). La muestra aleatoria PM mostró una correlación más débil, pero de todos modos estadísticamente significativa con respecto a la muestra cronometrada de 24 horas (correlación de Pearson, r = 0.404, p < 0.045). La muestra aleatoria AM mostró una correlación muy débil y estadísticamente no significativa (correlación de Pearson, r = 0. 05, p = 0.807) con respecto a la muestra cronometrada de 24 horas. De modo similar a la muestra en su totalidad, el análisis de género demostró que la excreción de sodio estimada de 24 horas en la muestra PM de 12 horas de las mujeres, tenía la mayor correlación (r = 0819, p < 0.001) con respecto a la excreción de sodio medida de 24 horas, seguida por las muestras de 12 horas AM (r = 0.793, p = 0.001) y las muestras PM al azar (r = 0.741, p = 0.02). La correlación entre las variables es más débil en los varones en comparación con las hembras. CONCLUSIÓN: En general, este estudio muestra una clara correlación entre la excreción de sodio estimada de 24 horas a partir de la muestra PM cronometrada de 12 horas, y la excreción de sodio medida de 24 horas. Estos hallazgos respaldan la idea de utilizar otras alternativas para determinar la excreción de sodio, teniendo en la mira el reemplazar la engorrosa recogida de orina de 24 horas por una muestra recogida en un tiempo menor. No obstante, una muestra de población más sólida y aleatoria, así como un método para corregir la variabilidad de la creatinina alta, son necesarios para mejorar aún más la importancia de los resultados obtenidos.

In vivo and in vitro anti-natriuretic activity of twigs fraction from Dorstenia picta: a possible mechanism

The present study examine the in vivo effects of Dorstenia Picta [D. picta] on urinary volume and sodium excretion in streptozotocin-induced diabetic rats, and determine a possible mechanism by which the extract increased sodium transport in A6 cells monolayers. Administration of the plant extract at the dose of 150 mg/kg during two weeks decreased urinary volume and sodium excretion. In vitro study showed that, apical application of the plant extract at the dose of 100 micro g/mL does not significantly increase sodium transport, whereas basolateral administration provoked a significant [P<0.05] increase of sodium transport in a concentration-dependent manner. The plant extract increases the sodium transport by 69.93% versus 55.41% for insulin and 78.44% for adenosine after 30 min. Preincubation of A6 cells monolayers with inhibitor of all adenosine receptors completely suppressed adenosine and plant extract stimulated sodium transport. Interesting is that, the A1 inhibitor receptor [DPCPX], at 100 nM completely abolished the effect of plant extract. The plant extract increased sodium transport by increase PI3-kinase activity and this effect is strongly inhibited by LY-294002. These data also suggest that, the twigs methanol fraction from Dorstenia picta increase sodium transport via PI 3-kinase pathway and requires A1 adenosine receptor

Rol del sistema kallicreína kinina y su interrelación con sistemas vasoactivos durante la preñez / Role of the kallikrein kinin system and its interrelationship with vasoactive systems in pregnancy

La hiperfiltración glomerular y el aumento de la reabsorción de sodio son factores fundamentales para el desarrollo de la unidad feto placentaria. Dichos factores resultan de adaptaciones hemodinámicas y renales en las que participan sistemas vasoactivos. Se pudo demostrar en ratas que la activación del sistema kallicreína kinina (SKK) precede a la instalación de la hiperfiltración glomerular, dado que su inhibición por aprotinina previene el aumento del filtrado glomerular. Además, la inhibición individual o asociada de los efectores específicos del SKK, las prostaglandinas (PGs) y el óxido nítrico (ON), confirman la dependencia del filtrado glomerular del SKK durante la preñez. Encontramos también que el sistema renina angiotensina (SRA) participa en la generación de la hiperfiltración glomerular dado que ésta es afectada por la administración de bloqueantes del SRA. La inhibición máxima sobre el pico de hiperfiltración se obtuvo con el bloqueo de ambos sistemas (SKK y SRA). Además, estrategias para alterar la hiperfiltración glomerular y la reabsorción de sodio de la preñez evidenciaron alteraciones en el desarrollo de la unidad feto placentaria, menor número de crías, mayor cantidad de reabsorciones intrauterinas y retardo en el crecimiento. El tratamiento combinado de inhibidores del SKK asociados a bloqueantes del SRA o de óxido nítrico mostraron los mayores efectos. En consecuencia, demostramos que el SKK juega un rol central en los fenómenos de adaptación que acompañan la preñez normal. La interrelación del SKK con varios sistemas vasoactivos parecería formar una red que participa en las adaptaciones hemodinámicas para un adecuado desarrollo de la gestación y de la unidad feto-placentaria.

Glomerular hyperfiltration and increased sodium reabsorption are key factors for the development of the fetus and placenta in pregnancy. These adjustments result from hemodynamic and renal factors involving vasoactive systems. It was demonstrated in rats that activation of KKS precedes the installation of glomerular hyperfiltration as aprotinin prevents the increase in glomerular filtration. In addition, individual or associated inhibition of specific kallikrein kinin system effectors, prostaglandins (PGs) and nitric oxide (NO), confirm the glomerular filtration rate dependence of KKS during pregnancy. It was also found that the renin-angiotensin system (RAS) contributes to glomerular hyperfiltration as this is affected by the administration of RAS blockers. The peak of hyperfiltration maximum inhibition was obtained by the blockade of both systems (KKS and RAS). In addition, strategies used to alter the glomerular hyperfiltration and increased sodium reabsorption during pregnancy, showed abnormalities in the development of the fetus and placenta, fewer offspring, more fetus resorptions and intrauterine growth retardation. KKS inhibitors associated with RAS or nitric oxide blockers showed the greatest impact. As a consequence, it was demonstrated that KKS plays a central role in the adaptation phenomenom that accompanies normal pregnancy. The interplay of KKS with several vasoactive systems, seem to arrange a network involved in the hemodynamic adaptations to allow the proper development of pregnancy and the fetus and placenta.

Prenatally programmed hypertension: role of maternal diabetes

Epidemiological and experimental studies have led to the hypothesis of the fetal origin of adult diseases, suggesting that some adult diseases might be determined before birth by altered fetal development. Maternal diabetes subjects the fetus to an adverse environment that has been demonstrated to result in metabolic, cardiovascular and renal impairment in the offspring. The growing amount of obesity in young females in developed and some developing countries should contribute to increasing the incidence of diabetes among pregnant women. In this review, we discuss how renal and extrarenal mechanisms participate in the genesis of hypertension induced by a diabetic status during fetal development.

Gender-dependent effects of aging on the kidney

It is well known that the kidney plays an important role in the development of cardiovascular diseases such as hypertension. The normal aging process leads to changes in kidney morphology, hemodynamics and function, which increase the incidence of cardiovascular events in the elderly population. These disturbances are influenced by several factors, including gender. In general, females are protected by the effects of estrogens on the cardiorenal system. Several studies have demonstrated the beneficial effects of estrogens on renal function in the elderly; however, the relationships between androgens and kidney health during one’s lifetime are not well understood. Sex steroids have many complex actions, and the decline in their levels during aging clearly influences kidney function, decreases the renal reserve and facilitates the development of cardiovascular disorders. Therefore, in this review, we discuss the cellular, biochemical, and molecular mechanisms by which sex hormones may influence renal function during the aging process.

Involvement of catecholaminergic medullary pathways in cardiovascular responses to acute changes in circulating volume

Water deprivation and hypernatremia are major challenges for water and sodium homeostasis. Cellular integrity requires maintenance of water and sodium concentration within narrow limits. This regulation is obtained through engagement of multiple mechanisms and neural pathways that regulate the volume and composition of the extracellular fluid. The purpose of this short review is to summarize the literature on central neural mechanisms underlying cardiovascular, hormonal and autonomic responses to circulating volume changes, and some of the findings obtained in the last 12 years by our laboratory. We review data on neural pathways that start with afferents in the carotid body that project to medullary relays in the nucleus tractus solitarii and caudal ventrolateral medulla, which in turn project to the median preoptic nucleus in the forebrain. We also review data suggesting that noradrenergic A1 cells in the caudal ventrolateral medulla represent an essential link in neural pathways controlling extracellular fluid volume and renal sodium excretion. Finally, recent data from our laboratory suggest that these structures may also be involved in the beneficial effects of intravenous infusion of hypertonic saline on recovery from hemorrhagic shock.