Torsemida em Comparação com Furosemida no Tratamento da Insuficiência Cardíaca: Uma Revisão Sistemática e Metanálise de Ensaios Clínicos Randomizados / Torsemide versus Furosemide in the Treatment of Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Resumo A furosemida é o diurético mais utilizado para o tratamento de sintomas de sobrecarga de volume em pacientes com insuficiência cardíaca. Dados recentes sugerem que a torsemida pode ser superior à furosemida neste contexto. No entanto, ainda não é claro se isso se traduz em melhores resultados clínicos nesta população. Avaliar se a torsemida é superior à furosemida no contexto da insuficiência cardíaca. Realizamos uma revisão sistemática e metanálise de estudos clínicos randomizados (ECRs) comparando a eficácia da torsemida em comparação com a furosemida em pacientes com insuficiência cardíaca. PubMed, Embase e Web of Science foram as bases de dados pesquisadas em busca de estudos elegíveis. Os desfechos de interesse foram internações por todas as causas, internações por insuficiência cardíaca (IIC), internações por todas as causas cardiovasculares, mortalidade por todas as causas, e melhoria de classe da NYHA. Parâmetros ecocardiográficos também foram avaliados. Foi aplicado um modelo de efeitos aleatórios para calcular as razões de risco (RR) e as diferenças médias (DM) com intervalos de confiança (IC) de 95% e nível de significância de 0,05. Foram incluídos 12 ECRs, envolvendo 4.115 pacientes. A torsemida reduziu significativamente a IIC (RR de 0,60; IC de 95%, 0,43-0,83; p=0,002; I2=0%), internação por causas cardiovasculares (RR de 0,72; IC de 95%, 0,60-0,88; p=0,0009; I2=0%), e melhora da fração de ejeção do ventrículo esquerdo (FEVE) (DM de 4,51%; IC de 95%, 2,94 a 6,07; p<0,0001; I2=0%) em comparação com a furosemida. Não houve diferença significativa no número de internações por todas as causas (RR de 0,93; IC de 95%, 0,86-1,00; p=0,04; I2=0%), mortalidade por todas as causas (RR de 0,98; IC de 95%, 0,87-1,10; p=0,73; I2=0%), melhora da classe NYHA (RR de 1,25; IC de 95%, 0,92-1,68; p=0,15; I2=0%), ou mudança de classe NYHA (DM de -0,04; IC de 95%, -0,24 a 0,16; p=0,70; I2=15%) entre os grupos. A torsemida reduziu significativamente as internações por insuficiência cardíaca e causas cardiovasculares, melhorando também a FEVE.

Abstract Furosemide is the most used diuretic for volume overload symptoms in patients with heart failure (HF). Recent data suggested that torsemide may be superior to furosemide in this setting. However, whether this translates into better clinical outcomes in this population remains unclear. To assess whether torsemide is superior to furosemide in the setting of HF. We performed a systematic review and meta-analysis of RCTs comparing the efficacy of torsemide versus furosemide in patients with HF. PubMed, Embase, and Web of Science were searched for eligible trials. Outcomes of interest were all-cause hospitalizations, hospitalizations for HF (HHF), hospitalizations for all cardiovascular causes, all-cause mortality, and NYHA class improvement. Echocardiographic parameters were also assessed. We applied a random-effects model to calculate risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) and a 0.05 level of significance. 12 RCTs were included, comprising 4,115 patients. Torsemide significantly reduced HHF (RR 0.60; 95% CI, 0.43-0.83; p=0.002; I2=0%), hospitalization for cardiovascular causes (RR 0.72; 95% CI, 0.60-0.88; p=0.0009; I2=0%), and improved LVEF (MD 4.51%; 95% CI, 2.94 to 6.07; p<0.0001; I2=0%) compared with furosemide. There was no significant difference in all-cause hospitalizations (RR 0.93; 95% CI, 0.86-1.00; p=0.04; I2=0%), all-cause mortality (RR 0.98; 95% CI, 0.87-1.10; p=0.73; I2=0%), NYHA class improvement (RR 1.25; 95% CI, 0.92-1.68; p=0.15; I2=0%), or NYHA class change (MD -0.04; 95% CI, -0.24 to 0.16; p=0.70; I2=15%) between groups. Torsemide significantly reduced hospitalizations for HF and cardiovascular causes, also improving LVEF.

Comparison of Diuretic and Electrolyte Excretory Activity between Compounds of Okra Fruit (Abelmoschus esculentus) and Furosemide

@#Introduction: Hypertension takes place of being one of the most concerning health issues, leading to increasing rate of death due to its complications. Pharmacological therapy diuretic become one to intervene on hypertension’s pathological sequences through sodium and potassium regulation. Similar diuretic effect can be achieved through fruits and vegetables crop including Okra fruit (Abelmoschus esculentus). Objective: to investigate the diuretic variance of different part of Okra fruit’s (Abelmoschus esculentus). Methods: In total of 8 groups of male Rattus norvegicus rats are sorted into control and intervention groups. As control, the C- Group (negative control group) was given Na- CMC 0.5% suspension, and C+ Group (positive control group) was given furosemide. The experimental groups P1, P2, and P3 were given Okra (Abelmoschus esculentus) whole fruit ethanolic extract; P4, P5, and P6 Group are were given Okra (Abelmoschus esculentus) seedless fruit ethanolic extract within range concentration of 75-300 mg/ kg body weight. Urine volume is measured every hour for 6 hours and the 24th hour. Sodium and potassium measurements are executed towards 24-hour urine accumulation. Results: Single dose administration of Okra (Abelmoschus esculentus) fruit significantly increase 5th hour urine volume as compared to furosemide (p < 0.001). Whole fruit of Okra (Abelmoschus esculentus) compared to seedless fruit exhibit no significant increment of urine volume and electrolytes (p > 0.05). Conclusion: Ethanolic extract of Okra (Abelmoschus esculentus) fruit produce similar diuretic effect to furosemide. However, seedless Okra (Abelmoschus esculentus) fruit exerts a higher kaliuretic effect compared to whole fruit and furosemide.

Sodium, potassium food intake and global cardiovascular risks in Togo

Objectives. To assess urinary sodium/potassium intake and identify its links with global cardiovascular risk (RCVG) according to the WHOPEN approach to WHO/ISH (International High Blood Pressure Society). Methods. It was a cross-sectional and analytical study that took place from July 6, 2020, to September 17, 2021, in Togo, in the Aneho, Notse and Dapaong localities. It focused on 400 adults selected by sampling. The analysis of two urine samples was done. Cardiovascular risk scores were determined from specific graphs that take into account age, gender, systolic blood pressure, diabetes status and smoking behavior. Results. Among the 400 respondents, 49% lived in rural areas. The average age was 41 (30; 51) years. The average sodium and potassium intakes were respectively 3.2 g (1.04-5.99) or 7.95 g of salt and 1.4 g (1.89-5.62) per day. The risk of excessive sodium intake was 2.39 times higher in urban areas than in rural ones (p=0.049). Residing in rural areas was associated with high potassium intakes compared to urban ones (OR=3,2 IC [1.89-5.62]). Thirteen percent (13%) of respondents were likely to develop at least a deadly or non-deadly cardiovascular disease in the next 10 years 'time, of whom 5% present a high risk. Excessive sodium intake increases by 2.10 times the risk of a deadly cardiovascular disease occurrence. Conclusions. Sodium intakes are high while potassium intakes are low with a subsequent global cardiovascular risk (GCVR) in the three cities. Sodium intakes were associated with VCVR. It is necessary to take steps to reduce excessive sodium intake and improve potassium intake.

Sodium and Potassium Urinary Excretion Among Malaysian Adults Claiming to Practice Salt-control: Findings from the Malaysian Community Salt Survey (MyCoSS)

@#Introduction: Raised blood pressure is associated with diet high in sodium and low in potassium. According to the Malaysian Community Salt Survey (MyCoSS), Malaysian adults consume a high sodium diet, despite half claiming that they control their salt intake. The objective of this study was to investigate the association of sodium and potassium with salt-control claims among adults from the MyCoSS study based on 24-h urinary excretion. Methods: Data of 1,047 respondents aged 18 years and above who completed the knowledge, attitude, and practice (KAP) questionnaire were used in this study. Face-to-face interviews were conducted to acquire information on sociodemographic, medical reports and KAP on salt intake. Sodium and potassium level were assessed from 24-hr urine specimen, anthropometric measurements were done using WHO criteria, while blood pressure was measured using validated digital blood pressure monitor. Descriptive and analysis of variance (ANOVA) were used to determine the associations between urinary sodium and potassium with salt-control claims and practices. Results: The consumption of sodium was higher than recommended, while potassium was lower among respondents who claimed to control their salt intake. Significant associations were found between sodium intake with marital status, ethnicity, education level and employment status. Meanwhile, significant associations were found between potassium intake with ethnicity and employment status. Conclusion: Sodium intake was high, and potassium intake was low among respondents who claimed they control their salt intake. Further study with detailed intervention on specific target group is required to improve sodium and potassium intakes among Malaysian adults.

The extent of involvement of ouabain, hippocampal expression of Na+/K+-ATPase, and corticosterone/melatonin receptors ratio in modifying stress-induced behavior differs according to the stressor in context

The aim of this study was to assess the effect of two types of stressors, regarding the extent of involvement of ouabain (OUA), hippocampal sodium/potassium ATPase (NKA) expression, and the hippocampal corticosterone receptors (CR)/melatonin receptors (MR) expression ratio, on the behavioral and cardiovascular responses and on the hippocampal cornu ammonis zone 3 (CA3) and dentate gyrus (DG). Thirty adult male Wistar albino rats aged 7-8 months were exposed to either chronic immobilization or a disturbed dark/light cycle and treated with either ouabain or vehicle. In the immobilized group, in the absence of hippocampal corticosterone (CORT) changes, rats were non-responsive to stress, despite experiencing increased pulse rate, downregulated hippocampal sodium/potassium pump, and enhanced hippocampal CR/MR expression ratio. Prolonged darkness precipitated a reduced upright attack posture, with elevated CORT against hippocampal MR downregulation. Both immobilization and, to a lesser extent, prolonged darkness stress resulted in histopathological and ultrastructural neurodegenerative changes in the hippocampus. OUA administration did not change the behavioral resilience in restrained rats, despite persistence of the underlying biochemical derangements, added to decreased CORT. On the contrary, with exposure to short photoperiods, OUA reverted the behavior towards a combative reduction of inactivity, with unvaried CR/MR and CORT, while ameliorating hippocampal neuro-regeneration, with co-existing NKA and MR repressions. Therefore, the extent of OUA, hippocampal NKA expression, and CR/MR expression, and subsequent behavioral and cardiac responses and hippocampal histopathology, differ according to the type of stressor, whether immobilization or prolonged darkness.

Trastornos electrolíticos inducidos por fármacos y sustancias tóxicas / Electrolyte disorders induced by drugs and toxic substances

Las enfermedades pueden generar un desequilibrio de electrolitos como parte de su fisiopatología, al igual que los medicamentos usados crónicamente y algunas sustancias tóxicas disponibles en nuestro medio. A pesar de todos los datos estadísticos existentes, la incidencia global de los trastornos electrolíticos secundarios a fármacos o sustancias tóxicas permanece desconocida, y, posiblemente, subregistrada; por lo tanto, el objetivo de esta revisión es analizar los trastornos electrolíticos que causan algunos medicamentos y sustancias tóxicas, y describir el mecanismo a través del cual se producen las alteraciones, en particular, del sodio, potasio, magnesio, calcio y fósforo, con el fin de alertar a los profesionales de la salud en el momento de enfrentarse a este tipo de condiciones en su práctica clínica. El conocimiento de los efectos adversos relacionados con medicamentos y tóxicos es importante para prevenir, identificar y gestionar de forma eficaz, complicaciones que son potencialmente peligrosas. Esta revisión pretende ser un referente de apoyo para los profesionales de la salud en estas situaciones

Diseases can generate an electrolyte imbalance as part of their pathophysiology, as well as chronic use of some medications, and toxic substances available in our environment. Despite all the separate statistical data, the overall incidence of fluid and electrolyte disorders secondary to drugs or toxic substances remains unknown, and possibly underreported; therefore, the objective of this review is to analyze electrolyte disorders caused by some medications and toxic substances, and describe the mechanism through which changes in sodium, potassium, magnesium, calcium and phosphorus occur, in particular, in order to alert health professionals when facing this type of conditions in their clinical practice. Knowledge of drug and toxic-related adverse effects is important to effectively prevent, identify, and manage complications that can be potentially life-threatening. This review intends to be a reference for supporting health professionals in these situations

The association between dietary sodium intake and the risk of cataract: data from Korean National Health and Nutrition Examination Survey 2012 / 한국영양학회지

PURPOSE: Sodium intake is known to be a critical dietary factor in several diseases including cataract. Earlier studies have reported that excess intake of sodium may elevate the risk of cataract. However, little is known about this in Koreans. Thus, the purpose of this study was to examine whether dietary intake of sodium and potassium might modify the risk of cataract. METHODS: A total of 1,319 males (219 cases) and 1,966 females (369 cases) from Korean National Health and Nutrition Examination Survey 2012 were analyzed. Energy adjusted dietary intakes of sodium and potassium and their ratios were evaluated to ascertain their associations with the risk of cataract. Dietary intake levels were stratified into quartiles and their risk modifying effects were estimated with logistic regression models with or without subjects' socio-economic characteristics and life styles for each sex. RESULTS: Findings suggested that various descriptive factors were associated with the risk of cataract either in males or females. Males' intake levels of sodium and potassium and their ratios did not differ between phenotypes. Higher intakes or higher ratio was not associated with the risk of cataract. In contrast, female controls had higher intakes of sodium and potassium. Higher intake of potassium reduced the risk of cataract in females. However, such association was not retained when subjects' socioeconomic status and life styles were factored into the analysis. CONCLUSION: Dietary sodium and potassium intakes minimally affected the risk of cataract in Korean males and females. More studies are needed to ascertain the true pathological effect of sodium intake on cataract aetiology.

Galangin ameliorates changes of membrane-bound enzymes in rats with streptozotocin-induced hyperglycemia

Objective: To assess the protective effect of galangin on membrane bound enzymes in rats with streptozotocin-induced diabetes. Methods: A single low dose of streptozotocin was injected to adult male albino rats to induce hyperglycemia. Galangin (8 mg/kg) or glibenclamide 600 μg/kg as a standard drug was given orally once daily for 45 days by gavage. Membrane-bound adenosine triphosphatases were determined including total ATPase, sodium-potassium-ATPase, calcium-ATPase and magnesium-ATPase in erythrocytes and tissues (kidney, liver, and heart). Results: The levels of total ATPases, sodium-potassium-ATPase, calcium-ATPase and magnesium-ATPase in erythrocytes and tissues were significantly altered in diabetic rats as compared to that in normal rats. After 45 days of treatment with galangin or glibenclamide, the levels of these enzymes were similar to that of normal control rats. Conclusions: Oral administration of galangin or glibenclamide can improve activities of these membrane-bound ATPases towards normal levels. Mechanism of galangin needs to be further explored in future.

Expression of NKCC1 and Na-K-ATPase in C57BL/6J mice with age-related hearing loss / 中国耳鼻咽喉头颈外科

OBJECTIVE Disturbance of K+ ion balance in inner ear is associated in age-related hearing loss. Our study is to investigate the role of NKCC1 and Na-K-ATPase in cochlea and auditory function regulated by with different expression of NKCC1 and Na-K-ATPase. METHODS Auditory threshold of young or old C57BL/6J mice was measured by auditory brainstem response(ABR). The expression of NKCC1 and Na-K-ATPase in mice cochlea were evaluated by reverse transcription polymerase chain reaction(RT-PCR) and western blotting. Furosemide and Ouabain were applied in vivo to inhibit NKCC1 and Na-K-ATPase in C57BL/6J mice. RESULTS C57BL/6J mice developed hearing loss at 12M by ABR threshold shifting to (75±10), (78±26) and (81±14)dB SPL at frequencies of 8, 16 and 32 kHz; PCR showed that the relative expression of NKCC1 and Na-K-ATPase mRNA in the aged group decreased, which were 0.52±0.06 and 0.35±0.04 times higher than those in the young control group, the difference was statistically significant(t =7.466 and 16.11, all P＜0.05). WB showed that relative expression of NKCC1 and Na-K-ATPase protein level in the aged group decreased by 0.79±0.02 and 0.68±0.05 times as much as that of the young control group, the difference was statistically significant(t =8.857 and 6.771, P all＜0.05). After applied with Furosemide and Ouabain to suppress the two ion transporters, the ABR threshold increased to (50±17), (53±21), (55±17)dB SPL and (56±6), (70±17), (73±6)dB SPL at frequencies of 8, 16 and 32 kHz. CONCLUSION In vivo experiment of C57BL/6J suggested that NKCC1 and Na-K-ATPase might be related to age related hearing loss.

Galangin ameliorates changes of membrane-bound enzymes in rats with streptozotocin-induced hyperglycemia

Objective: To assess the protective effect of galangin on membrane bound enzymes in rats with streptozotocin-induced diabetes. Methods: A single low dose of streptozotocin was injected to adult male albino rats to induce hyperglycemia. Galangin (8 mg/kg) or glibenclamide 600 μg/kg as a standard drug was given orally once daily for 45 days by gavage. Membrane-bound adenosine triphosphatases were determined including total ATPase, sodium-potassium-ATPase, calcium-ATPase and magnesium-ATPase in erythrocytes and tissues (kidney, liver, and heart). Results: The levels of total ATPases, sodium-potassium-ATPase, calcium-ATPase and magnesium-ATPase in erythrocytes and tissues were significantly altered in diabetic rats as compared to that in normal rats. After 45 days of treatment with galangin or glibenclamide, the levels of these enzymes were similar to that of normal control rats. Conclusions: Oral administration of galangin or glibenclamide can improve activities of these membrane-bound ATPases towards normal levels. Mechanism of galangin needs to be further explored in future.

Baseline survey of sodium,potassium and blood pressure of adult inhabitants in Liandu District / 预防医学

Objective@#To investigate the sodium,potassium and blood pressure of adult residents in Liandu District of Lishui,and to provide evidence for salt reduction intervention.@*Methods@#A stratified random sampling method was used to select residents aged 18 to 69 years in Liandu District from December 2016 to February 2017. A questionnaire survey and physical examination were conducted to collect basic information. The 24-hour urine samples were collected to detect sodium and potassium intake.@*Results@#Among 300 participants,the average daily intake of sodium was（10.59±3.90）g,which was higher in men than in women [（11.11±4.33）g vs.（10.08±3.37）g,P<0.05]. There were 274 participants with average daily intake of sodium more than 6 g,accounting for 91.33%. The average daily intake of potassium was（1.67±0.71）g,which was higher in women than in men [（1.77±0.72）g vs.（1.57±0.68）g,P<0.05]. The average daily intakes of potassium were significantly different among different age groups,with participants aged 20 to 29 years the lowest（P<0.05）. There were 217 participants with average daily intake of potassium less than 2 g,accounting for 72.33%. The ratio of sodium to potassium was 4.7±2.2,which was higher in men than in women（5.3±2.7 vs. 4.1±1.4,P<0.05）and decreased with age（P<0.05）. There were 291 participants with the ratio more than 1.87,accounting for 97.00%. The prevalence of hypertension was 31.67%,which was 33.65% in men and 29.80% in women.@*Conclusion@#The residents in Liandu District have high intake of sodium and prevalence of hypertension,yet low intake of potassium.

Phenotypic and genotypic characteristics of fever-induced paroxysmal weakness and encephalopathy caused by ATP1A3 pathogenic variants / 中华儿科杂志

Objective@#To characterize fever-induced paroxysmal weakness and encephalopathy (FIPWE) caused by ATP1A3 gene pathogenic variant.@*Methods@#Phenotypic and genotypic characteristics of 4 FIPWE patients (3 boys and 1 girl), who were ascertained from October 2016 to March 2018 in Beijing Children's Hospital due to ATP1A3 heterozygous variants, were retrospectively analyzed. The whole exsome sequencing was used for genetic testing.@*Results@#The onset ages of 4 patients were 2 years and 9 months, 2 years and 4 months, 8 months, 2 years and 5 months respectively. The episode ranged from 1 to 3 times, and at 3 months to 2 years and 10 months intervals. All 4 patients had symptoms of limb weakness and encephalopathy, accompanied with mild to severe ataxia or athetosis. The tendon reflex was absent in all patients, and the Babinski's sign was positive. Three patients had dysphagia and 3 patients had slurred speech. Three patients had abnormal eye movements, including strabismus and opsoclonus. None of the 4 patients exhibited visual impairment, auditory impairment or talipes cavus. The duration of acute phase ranged from 1 week to 3 months. In 3 relapsing patients, symptoms became progressively worse, with relapses occurring frequently and recovery being more difficult, and various sequelae were found after the last relapse. All patients carried heterozygous variant in ATP1A3 gene. The missense variants result in the substitution of an arginine residue at position 756. Three variants were identified, including C. 2267G > T (p. R756L) (1 case), C. 2266C > T (p. R756C) (2 cases), and C. 2267G > A (p. R756H) (1 case). Three were de novo and one inherited from his father, but the grandparents did not carry the variant. All variants were reported as pathogenic.@*Conclusions@#FIPWE is one of new clinical phenotypes of ATP1A3 spectrum disease and most cases are sporadic. The missense variants result in the substitution of an arginine residue at position 756. This report provided insights into the phenotype-genotype association in patients with FIPWE caused by pathogenic variants of ATP1A3.

Effect of different crystalloids on internal environment in patients with septic shock receiving early fluid resuscitation: a prospective randomized controlled trial / 中华危重病急救医学

Objective To compare the effect of 0.9％ NaCl solution, Ringer solution, and acetate sodium potassium magnesium calcium glucose solution (ASPMCG solution) on internal environment in patients with septic shock receiving early fluid resuscitation.Methods A prospective randomized controlled trial was conducted. From June 2016 to January 2018, a total of 280 patients with septic shock admitted to intensive care unit (ICU) of Northern Jiangsu People's Hospital were enrolled. All eligible patients were randomly divided into 0.9％ NaCl solution group (group N), Ringer solution group (group L) and ASPMCG solution group (group P) with random number table. In all patients, catheters were placed in the right internal jugular vein or subclavian vein and were infused with 30 mL/kg of corresponding crystalloid within 3 hours after admission. According to fluid responsiveness, the rehydration rate and fluid volume were determined by the researcher within 6 hours. Other treatments were based on the 2012 Surviving Sepsis Campaign (SSC) guidelines during the study. In this study, 6-hour or 24-hour fluid volume and 7-day exogenous insulin use were recorded. The changes in arterial blood pH, base excess (BE), blood glucose (Glu), lactic acid (Lac), and serum Na+, K+, Cl-, Ca2+ were observed at 0, 3, 6, 24 hours, and 3 days and 7 days of resuscitation.Results In this study, a total of 1082 patients were admitted to the ICU, and patients who did not meet the diagnostic criteria for septic shock, death or discharge within 24 hours of ICU admission were excluded. Finally, 280 patients with septic shock were enrolled in the analysis, with 94 patients in group N, 94 patients in group L and 92 patients in group P. There was [Abstract] Objective To compare the effect of 0.9％ NaCl solution, Ringer solution, and acetate sodium potassium magnesium calcium glucose solution (ASPMCG solution) on internal environment in patients with septic shock receiving early fluid resuscitation.Methods A prospective randomized controlled trial was conducted. From June 2016 to January 2018, a total of 280 patients with septic shock admitted to intensive care unit (ICU) of Northern Jiangsu People's Hospital were enrolled. All eligible patients were randomly divided into 0.9％ NaCl solution group (group N), Ringer solution group (group L) and ASPMCG solution group (group P) with random number table. In all patients, catheters were placed in the right internal jugular vein or subclavian vein and were infused with 30 mL/kg of corresponding crystalloid within 3 hours after admission. According to fluid responsiveness, the rehydration rate and fluid volume were determined by the researcher within 6 hours. Other treatments were based on the 2012 Surviving Sepsis Campaign (SSC) guidelines during the study. In this study, 6-hour or 24-hour fluid volume and 7-day exogenous insulin use were recorded. The changes in arterial blood pH, base excess (BE), blood glucose (Glu), lactic acid (Lac), and serum Na+, K+, Cl-, Ca2+ were observed at 0, 3, 6, 24 hours, and 3 days and 7 days of resuscitation.Results In this study, a total of 1082 patients were admitted to the ICU, and patients who did not meet the diagnostic criteria for septic shock, death or discharge within 24 hours of ICU admission were excluded. Finally, 280 patients with septic shock were enrolled in the analysis, with 94 patients in group N, 94 patients in group L and 92 patients in group P. There was no significant difference in the amount of crystalloid, colloidal fluid, total fluid within 6 hours or 24 hours or exogenous insulin dose within 7 days among the three groups. After fluid resuscitation, blood Cl- concentration in the three groups was increased in different degrees, peaked at 24 hours, but it in group N was significantly higher than that in group L and group P (mmol/L: 107.5±5.6 vs. 106.1±4.8, 105.1±4.2, bothP ﹤ 0.05). Moreover, blood Ca2+concentration also showed an increased tendency, it was significantly lower at 3 hours and 6 hours in group N than that in group L and group P (mmol/L: 1.10±0.08 vs. 1.15±0.09, 1.12±0.10 at 3 hours, 1.12±0.10 vs. 1.16±0.08, 1.15±0.09 at 6 hours, all P < 0.05). There was no significant difference in blood Cl- or Ca2+between groups L and P (bothP > 0.05). Arterial blood pH, BE, Glu, Lac, Na+, or K+at each time point during fluid resuscitation also showed no difference among the three groups.Conclusion Among patients with septic shock receiving early fluid resuscitation, compared with Ringer solution and ASPMCG solution, 0.9％ NaCl solution may cause hyperchloremia and hypocalcemia, but has no significant effect on acid-base balance.Clinical Trial Registration Chinese Clinical Trial Registry, ChiCTR-IOR-16009176.

Effect of sevoflurane on activities of Na+-K+-ATPase and Ca2+-ATPase in hippocampus of diabetic rats / 中华麻醉学杂志

Objective To evaluate the effect of sevoflurane on activities of Na+-K+-ATPase and Ca2+-ATPase in the hippocampus of diabetic rats.Methods SPF healthy male Wistar rats,aged 8 weeks,weighing 180-200 g,were fed a high-fat diet for 3 consecutive weeks and streptozotocin was intraperitoneal-ly injected to induce type 2 diabetes mellitus.Forty-four rats with diabetes mellitus were divided into 2 groups (n=22 each) using a random number table:diabetic group (D group) and sevoflurane group (S group).Another 22 healthy Wistar rats,aged 8 weeks,weighing 180-200 g,served as control group (C group).Oxygen was inhaled for 2 h in C and D groups,and 2.4％ sevoflurane was inhaled for 2 h in S group.Eight rats were sacrificed at 30 min after treatment,brains were removed and hippocampi were isolated for measurement of Na+-K+-ATPase and Ca2+-ATPase activities in hippocampal tissues by spectrophotometry.Ten rats were randomly selected at 1 day after treatment,and Morris water maze test was performed to assess the cognitive function.Four rats were randomly sacrificed,brains were removed and hippocampi were isolated for examination of the mitochondrial ultrastructure with a transmission electron microscope.Results Compared with group C,the escape latency was significantly prolonged,the number of crossing the original platform was reduced,the percentage of time of staying at the original platform quadrant was decreased,the activities of Na+-K+-ATPase and Ca2+-ATPase in hippocampi were decreased (P＜ 0.05),and mitochondrial swelling and decreased mitochondrial cristae were observed under the electron microscope in group D.Compared with group D,the escape latency was significantly prolonged,the number of crossing the original platform was reduced,the percentage of time of staying at the original platform quadrant was decreased,the activities of Na+-K+-ATPase and Ca2+-ATPase in hippocampi were decreased (P＜ 0.05),and mitochondrial swelling and vacuolization were found under the electron microscope in group S.Conclusion The mechanism by which sevoflurane aggravates cognitive dysfunction is related to deceasing activities of Na+-K+-ATPase and Ca2+-ATPase in the hippocampus of diabetic rats.

The Effects of Altered Membrane Cholesterol Levels on Sodium Pump Activity in Subclinical Hypothyroidism

BACKGROUND: Metabolic dysfunctions characteristic of overt hypothyroidism (OH) start at the early stage of subclinical hypothyroidism (SCH). Na⁺/K⁺-ATPase (the sodium pump) is a transmembrane enzyme that plays a vital role in cellular activities in combination with membrane lipids. We evaluated the effects of early changes in thyroid hormone and membrane cholesterol on sodium pump activity in SCH and OH patients. METHODS: In 32 SCH patients, 35 OH patients, and 34 euthyroid patients, sodium pump activity and cholesterol levels in red blood cell membranes were measured. Serum thyroxine (T₄) and thyroid stimulating hormone (TSH) levels were measured using enzyme-linked immunosorbent assays. Differences in their mean values were analysed using post hoc analysis of variance. We assessed the dependence of the sodium pump on other metabolites by multiple regression analysis. RESULTS: Sodium pump activity and membrane cholesterol were lower in both hypothyroid groups than in control group, OH group exhibiting lower values than SCH group. In SCH group, sodium pump activity showed a significant direct dependence on membrane cholesterol with an inverse relationship with serum TSH levels. In OH group, sodium pump activity depended directly on membrane cholesterol and serum T4 levels. No dependence on serum cholesterol was observed in either case. CONCLUSION: Despite the presence of elevated serum cholesterol in hypothyroidism, membrane cholesterol contributed significantly to maintain sodium pump activity in the cells. A critical reduction in membrane cholesterol levels heralds compromised enzyme activity, even in the early stage of hypothyroidism, and this can be predicted by elevated TSH levels alone, without any evident clinical manifestations.

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.

Prediction of Cortical Defect Using C-Reactive Protein and Urine Sodium to Potassium Ratio in Infants with Febrile Urinary Tract Infection

PURPOSE: We investigated whether C-reactive protein (CRP) levels, urine protein-creatinine ratio (uProt/Cr), and urine electrolytes can be useful for discriminating acute pyelonephritis (APN) from other febrile illnesses or the presence of a cortical defect on 99mTc dimercaptosuccinic acid (DMSA) scanning (true APN) from its absence in infants with febrile urinary tract infection (UTI). MATERIALS AND METHODS: We examined 150 infants experiencing their first febrile UTI and 100 controls with other febrile illnesses consecutively admitted to our hospital from January 2010 to December 2012. Blood (CRP, electrolytes, Cr) and urine tests [uProt/Cr, electrolytes, and sodium-potassium ratio (uNa/K)] were performed upon admission. All infants with UTI underwent DMSA scans during admission. All data were compared between infants with UTI and controls and between infants with or without a cortical defect on DMSA scans. Using multiple logistic regression analysis, the ability of the parameters to predict true APN was analyzed. RESULTS: CRP levels and uProt/Cr were significantly higher in infants with true APN than in controls. uNa levels and uNa/K were significantly lower in infants with true APN than in controls. CRP levels and uNa/K were relevant factors for predicting true APN. The method using CRP levels, u-Prot/Cr, u-Na levels, and uNa/K had a sensitivity of 94%, specificity of 65%, positive predictive value of 60%, and negative predictive value of 95% for predicting true APN. CONCLUSION: We conclude that these parameters are useful for discriminating APN from other febrile illnesses or discriminating true APN in infants with febrile UTI.

Primary hypoadrenocorticism in a dog / Hipoadrenocorticismo primário em um cão / Hipoadrenocorticismo primario en un perro

This report describes the clinical and laboratorial findings as well as the therapeutic protocol performed in a three-year-old mongrel female intact dog, referred to the Veterinary Hospital of FAMEZ/UFMS. The animal had a previous history of recurrent gastrointestinal signs (such as lethargy, vomiting, loss of appetite, melena and abdominal pain), acute crisis episodes, bradycardia, hypotension, hypothermia and increase of capillary refill time, recognized as addisonian crisis due to primary hypoadrenocorticism. Laboratorial findings included anemia, eosinophilia, neutrophilia, lymphocytosis, sodium-potassium ratio of 14,02 mEq/L and prerenal azotemia. Based on that, it was confirmed the diagnosis of primary hypoadrenocorcitism. Thus, it was recommended supplementation therapy with mineralocorticoid (aldosterone) and glucocorticoid (cortisol) corresponding respectively, fludrocortisone acetate of 0.2 mg per kg of BW, by mouth, once daily and prednisone 0.2 mg per kg of BW, by mouth, twice daily until further recommendations. The prognostic was excellent, since the animal significantly improved body condition, andclinical signs disappeared after therapy which lead the sodium-potassium ratio to 35.11 mEq/L. Thus, the clinician must always suspect of primary hypoadrenocorticism in dogs with intermittent nonspecific signs that get better with support therapy. Presumably, hypoarenocorticism must be under diagnosed in veterinary medicine, reinforcing the need to require specific exams in patients that show this wax and wane feature of clinical signs.

O presente relato descreve os achados clínicos, laboratoriais e conduta terapêutica de um animal da espécie canina, fêmea, com três anos de idade, inteiro, sem raça definida, diagnosticado com hipoadrenocorticismo primário atendido no Hospital Veterinário da FAMEZ/UFMS. O animal apresentou histórico de recidivas de sinais gastrintestinais (letargia, vômitos, perda de apetite, melena e dor abdominal), crise adrenal aguda, bradicardia, hipotensão, hipotermia e aumento do tempo de preenchimento capilar. As alterações laboratoriais compreenderam linfocitose, anemia, eosinofilia, neutrofilia, densidade urinária < 1.030, relação sódio: potássio 14,02 mEq/L e azotemia pré-renal. Baseado nos achados clínicos-laboratoriais confirmou-se o hipoadrenocorticismo primário. Em seguida, foi instituído terapia de suplementação de mineralocorticoide (aldosterona) e glicocorticoide (cortisol), correspondendo respectivamente ao acetato de fludrocortisona na dose de 0,2 mg/kg por via oral uma vez ao dia e prednisona 0,2 mg/kg por via oral duas vezes por dia até novas recomendações. O prognóstico foi excelente para este caso, já que houve melhora significativa do animal, com o desaparecimento dos sinais clínicos e com nova relação sódio: potássio de 35,11 mEq/L. Assim, deve-se sempre suspeitar de hipoadrenocorticismo primário canino em pacientes com o curso de aparecimento e desaparecimento com sinais inespecíficos que melhorem com terapia de suporte. Presume-se que o hipoadrenocorticismo primário em cães seja subdiagnosticado na medicina veterinária, por isso a importância dos clínicos em suspeitar e solicitar exames específicos em pacientes que apresentam esse curso da doença.

El informe describe los hallazgos clínicos, de laboratorio y manejo terapéutico de un perro, hembra, con tres años de edad, entera, mestizo, con diagnóstico de hipoadrenocorticismo primario atendido en el Hospital Veterinario de la FAMEZ/UFMS. El animal tuvo un historial de signos gastrointestinales recurrentes (letargia, vómitos, pérdida de apetito, melena y dolor abdominal), crisis renal aguda, bradicardia, hipotensión, hipotermia y un aumento del tiempo de llenado capilar. Las alteraciones de laboratorio presentaron linfocitosis, anemia, eosinofilia, neutrofilia, densidad de la orina < 1,030, relación sodio: potasio 14,02 mEq/L y azotemia prerrenal. Con base en los hallazgos clínicos y de laboratorio, se confirmó el hipoadrenocorticismo primario. A continuación, se introdujo terapia con administración de mineralocorticoide (aldosterona) y glucocorticoide (cortisol), que correspondieron respectivamente al acetato de fludrocortisona a una dosis de 0,2mg/kg por vía oral una vez al día y prednisona 0,2 mg/kg por vía oral dos veces al día hasta nuevas recomendaciones. El pronóstico fue excelente para este caso, ya que hubo mejora significativa del animal, desapareciendo los signos clínicos y con una nueva relación sodio: potasio de 35,11 mEq/L. Por lo tanto, siempre se debe sospechar del hipoadrenocorticismo primario canino en pacientes con el curso de aparecimiento y desaparecimiento con signos inespecíficos que mejoran con terapia de soporte. Es posible que el hipoadrenocorticismo primario en perros sea diagnosticado en la medicina veterinaria, así la importancia de los clínicos en sospechar y solicitar exámenes específicos en pacientes que presentan ese curso de la enfermedad.

Aspectos clínicos, fisiopatológicos e genéticos das tubulopatias hereditárias na infância / Clinical, pathophysiological and genetic aspects of inherited tubular disorders in childhood

ResumoNesta revisão, descrevemos a função tubular de cada segmento do néfron seguida das descrições das principais alterações moleculares que possam ocorrer nos transportadores expressos nestes locais. Assim, o conhecimento das modificações na função tubular renal permite o entendimento e o reconhecimento clínico das doenças tubulares renais que podem causar a morte fetal, neonatal ou infantil. Além disso, as crianças com tubulopatias podem evoluir para doença renal crônica terminal numa fase precoce da vida e também podem apresentar distúrbios do crescimento e do desenvolvimento acompanhados ou não de alterações neurológicas. Então, nós utilizamos o unitermo "inherited tubular disorders" a fim de selecionar na base de dados do PubMed os estudos publicados desde 2006. Esperamos que a leitura desta revisão auxilie no rápido diagnóstico dos pacientes com tubulopatias, o que poderá permitir o tratamento especializado e a possível melhora do prognóstico e qualidade de vida destes indivíduos.

AbstractIn this review, we described the tubular function of each nephron segment followed by the most important changes that may occur in the transporters expressed therein. Thus, knowledge of the changes in renal tubular function allows the understanding and recognition of renal tubular diseases that can cause stillbirth or death in newborns or in childhood. Moreover, children with tubular disorders may progress to chronic renal disease at an early stage of life and they may also show disturbances of growth and development associate or not with neurological dysfunction. Therefore, we used the keyword "inherited tubular disorders" to select the children studies that have been published in the PubMed database since 2006. We hope that this review may help physicians to perform an early diagnosis in patients with tubular disorders allowing a specialized treatment and an improvement in their prognosis and quality of life.

Effects of percutaneous midband pulse current stimulation in hepatic region on the activity of hepatic mitochondrial Na+-K+-ATPase and Ca2+-Mg2+-ATPase in exercise-induced fatigued rats / 解放军医学杂志

Objective To explore the effects of percutaneous impulsive current stimulation in hepatic region on the activity of hepatic mitochondrial Na+-K+-ATPase and Ca2+-Mg2+-ATPase in exercise-induced fatigued rats, in order to investigate the effect of exercise-induced fatigue. Methods Seventy-two 8-week old male Wistar rats were randomly divided into 4 groups (18 each): control group (group A), fatigue group (group B), stimulation before fatigue group (group C) and stimulation after fatigue group (group D). Exhaustion of animals in B, C and D groups were reproduced by prolonged swimming. Current stimulation (1024Hz, 10mA, current cycle 1sec) for 20 minutes was given to the rats of group C before swimming, and to those in group D after exhaustion. At the weekend of 1st, 3rd and 5th week after modeling, the rats were sacrificed in batches from each group (6 each). The activities of hepatic mitochondrial Na+-K+-ATPase and Ca2+-Mg2+-ATPase were determined by spectrophotometry, and Bradfood protein quantification was employed to quantitate the protein in rats' hepatic mitochondria. Results No significant difference was found in swimming-exhaustion time among 3 groups at the first weekend (P>0.05), while the swimming-exhaustion time was significantly prolonged at the 3rd and 5th weekends in group D than in group B and C (P+-K+-ATPase and Ca2+-Mg2+-ATPase among the 4 groups (including group A) at the weekend of the 1st week (P>0.05), while the enzyme activities were obviously lower at the 3rd and 5th weekend in group B than that in groups A, C and D (P+-K+-ATPase and Ca2+-Mg2+-ATPase. Percutaneous pulsive current stimulating hepatic region of exercise-induced fatigued rats may improve the enzyme activity, reduce the concentration of free calcium and calcium overload in mitochondria, stimulate the oxidative phosphorylation, accelerate the rate of respiratory chain, promote exercise endurance and score, and relieve exercise-induced fatigue rapidly.