RESUMO
Sodium chloride (NaCl) confers a unique flavor and quality in meat products, however, due to growing concerns about the adverse effects of excessive NaCl consumption, how to reduce NaCl content while ensuring quality and safety has become a research hotspot in this field. This review mainly discusses the role of NaCl in dry-cured meat, as well as novel salt-reducing substances that can substitute for the effects of NaCl to achieve sodium reduction objectives. New technologies, such as vacuum curing, ultrahigh pressure curing, ultrasonic curing, pulsed electric field curing, and gamma irradiation, to facilitate the development of low-sodium products are also introduced. The majority of current salt reduction technologies function to enhance salt diffusion and decrease curing time, resulting in a decrease in NaCl content. Notably, future studies should focus on implementing multiple strategies to compensate for the deficiencies in flavor and safety caused by NaCl reduction.
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Produtos da Carne , Cloreto de Sódio , Cloreto de Sódio na Dieta , Carne , SódioRESUMO
Potassium (K) fertilizers are limited and non-renewable. Exploring the use of sodium (Na) and silicon (Si) as alternatives to reduce its use may be an alternative. However, the relationship of these elements with arugula nutrition and quality is unknown. Therefore, the objective of this study is to verify the effects of Na and Si on the parameters of arugula under conditions of K deficiency and sufficiency. The experiment was conducted in a greenhouse in a hydroponics system. The treatments used were K-sufficient, K-sufficient with Na, K-sufficient with Si, K-deficient, K-deficient with Na, and K-deficient with Si. Evaluations of physiological, biochemical, nutritional, and growth aspects were performed. Si supply increased the production of total phenols, ascorbic acid, and carotenoids in K-deficient plants. Both elements attenuated the damage caused by K deficiency and improved quality. This is an innovative strategy for the sustainable cultivation of this species.
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Deficiência de Potássio , Humanos , Silício , Sódio , Potássio , Ácido AscórbicoRESUMO
Profound hyponatraemia, defined as sodium <125 mmol/L, is a very rare complication of pre-eclampsia (PET) with a relative paucity of cases reported. Pre-eclampsia is a multisystem disorder with a maternal mortality of up to 20%. Hyponatraemia is associated with disease severity, twin pregnancy, advanced maternal age, in vitro fertilisation and HELLP (haemolysis, elevated liver enzymes and low platelets). The authors present the case of a low-risk nulliparous woman presenting with frontal headache and normal BP at 31+2 weeks gestation. Laboratory investigations confirmed a sodium of 123 mmol/L. Her urine protein creatinine ratio was 322 mg/mmol. She developed PET (BP 171/100 mm Hg) refractory to pharmacological management. She underwent an emergency lower segment caesarean section and was delivered of a live neonate. The maternal serum sodium normalised within 24 hours. Hyponatraemia should be regarded as a marker of severity in the setting of pre-eclampsia and may be an indication for an expedited delivery. Prompt management is required to prevent convulsions, maternal mortality and adverse fetal outcomes.
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Síndrome HELLP , Hiponatremia , Pré-Eclâmpsia , Feminino , Gravidez , Recém-Nascido , Humanos , Hiponatremia/etiologia , Cesárea , SódioRESUMO
OBJECTIVE: Type 2 diabetes mellitus (T2DM) is known to be associated with endothelial dysfunction (ED). Reducing ED can attenuate the occurrence of cardiovascular diseases. One of the indicators of ED is decreased coronary blood flow (CBF). Sodium-glucose co-transporter 2 inhibitors (SGLT-2is) are known to directly improve ED in both euglycemic and hyperglycemic conditions and have been shown to decrease the incidence of major cardiovascular events. We aimed to investigate whether SGLT-2is improves CBF in patients with T2DM, who have angiographically normal or nearly normal coronary arteries. PATIENTS AND METHODS: In this single-center retrospective study, all patients who underwent coronary angiography between January 2017 and September 2022 were screened. We designed the study by dividing the patients into two groups - those who used conventional antidiabetic medications (CAM) together with SGLT-2is (patients using an SGLT-2 inhibitor for at least 3 months) and those who used only conventional antidiabetic medications. Of the 18,205 patients who underwent coronary angiography, 5,040 patients had T2DM. After exclusion, 288 patients were divided into two groups - those who used CAM together with SGLT-2is and those who used only CAM. CBF was assessed by thrombolysis in myocardial infarction (TIMI) frame counting. RESULTS: Two hundred eighty-eight patients who had T2DM and met the inclusion criteria were included in our study. The patients were divided into two groups - those who used CAM together with SGLT-2is (n = 75) and those who used only CAM (n = 213). The median age in the group that used CAM together with SGLT-2is was 55 (51-64), where 52 (69.3%) patients were female. The mean TIMI frame count (TFC) was 23.5 in the group using CAM + SGLT-2is and 27.5 in the group using only CAM. In the multivariable linear regression analysis, the mean TFC was significantly lower in the group using CAM together with SGLT-2is compared to the group using only CAM [ß-coefficient = -12.766, 95% Cl: -5.304; -3.887, p < 0.001]. Moreover, there was a statistically significant correlation between an increase in BMI and hemoglobin with an increase in the mean TFC [ß-coefficient = 3.018, 95% Cl 0.037-0.175, p = 0.003 and ß-coefficient = 2.316, 95% Cl 0.033-0.405, p = 0.021, respectively]. CONCLUSIONS: We have demonstrated that the use of SGLT-2is improves coronary artery blood flow in patients with T2DM who have normal or nearly normal coronary angiography.
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Diabetes Mellitus Tipo 2 , Infarto do Miocárdio , Inibidores do Transportador 2 de Sódio-Glicose , Simportadores , Humanos , Feminino , Masculino , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Estudos Retrospectivos , Hipoglicemiantes , Glucose , SódioRESUMO
Diabetes mellitus (DM) is the leading cause of premature death and disability. Despite a significant number of drugs, the effectiveness of therapy aimed at normalizing the level of glycemia and preventing complications does not fully satisfy doctors and patients. Therefore, the search for new approaches for the prevention and treatment of DM and its complications continues. Significant resources are used to develop new drugs, but recently the possibility of using «old¼ widely available drugs with newly discovered pleiotropic properties has been substantiated. These may include preparations of gammaaminobutyric acid (GABA) and agents that directly or indirectly activate GABAergic transmission, which have a pronounced pancreatic protective effect, which has been widely discussed in foreign literature over the past 10-15 years. However, there are few such publications in the domestic literature.It has been established that the content of GABA in ß-cells in patients with type 1 and type 2 diabetes is reduced and this correlates with the severity of the disease. Genetic suppression of GABA receptors causes a significant decrease in the mass of ß-cells and glucose-stimulated insulin secretion, which confirms the importance of GABA in ensuring glucose homeostasis and the advisability of replenishing the GABA deficiency in DM with its additional administration. It has been established that in animals with DM, GABA suppresses apoptosis and stimulates the regeneration of ß-cells, increases ß-cell mass and insulin production.Experimental data have been obtained indicating a synergistic effect of GABA when combined with glucagon-like peptide-1 (GLP-1) receptor agonists, DPP-4 inhibitors and sodium-glucose cotransporter 2 (SGLT-2) inhibitors, when a more pronounced pancreoprotective effect is observed, due to decrease in oxidative and nitrosative stress, inflammation, increase in the level of Klotho protein, Nrf-2 activity and antioxidant defense enzymes, suppression of NF-kB activity and expression of pro-inflammatory cytokines. As a result, all this leads to a decrease in apoptosis and death of ß-cells, an increase in ß-cell mass, insulin production and, at the same time, a decrease in glucagon levels and insulin resistance.The review substantiates the feasibility of using GABA and drugs with a positive GABAeric effect in combination with new generation antidiabetic agents: GLP-1 receptor agonists, DPP-4 inhibitors and SGLT-2 inhibitors in order to increase their antidiabetic potential.The search was carried out in the databases Pubmed, eLibrary, Medline. Keywords: diabetes mellitus, gamma-aminobutyric acid, glucagon-like peptide-1, GLP-1 receptor agonists, glucose-dependent insulinotropic peptide, dipeptidyl peptidase inhibitors, sodium-glucose cotransporter 2 inhibitors. The search was carried out from 2000 to 2022, but the review presents the results studies published mainly in the last 3 years, due to the requirements of the journal for the maximum amount of work and the number of sources.
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Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Animais , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1 , Insulina , Ácido gama-Aminobutírico/farmacologia , Insulina Regular Humana , SódioRESUMO
INTRODUCTION: Sepsis is one of the most common risk factors for acute respiratory distress syndrome (ARDS). Neutrophil elastase (NE) is believed to be an important mediator of ARDS. When sepsis occurs, a large number of inflammatory factors are activated and released, which makes neutrophils migrate into the lung, eventually leading to the occurrence of ARDS. Sivelestat sodium is an NE inhibitor that can inhibit the inflammatory reaction during systemic inflammatory response syndrome and alleviate lung injury. Therefore, we hypothesise that intravenous sivelestat sodium may prevent the occurrence of ARDS in patients with sepsis. METHODS AND ANALYSIS: This is a prospective, investigator-initiated, double-blind, adaptive, multicentre, randomised, controlled clinical trial with an adaptive 'sample size re-estimation' design. Patients meeting the inclusion criteria who were transferred into the intensive care unit will be randomly assigned to receive sivelestat sodium or placebo for up to 7 days. The primary outcome is the development of ARDS within 7 days after randomisation. A total of 238 patients will be recruited based on a 15% decrease in the incidence of ARDS in the intervention group in this study. A predefined interim analysis will be performed to ensure that the calculation is reasonable after reaching 50% (120) of the planned sample size. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of ZhongDa Hospital affiliated to Southeast University (identifier: Clinical Ethical Approval No. 2021ZDSYLL153-P03). Results will be submitted for publication in peer-reviewed journals and presented at relevant conferences and meetings. TRIAL REGISTRATION NUMBER: NCT04973670.
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Síndrome do Desconforto Respiratório , Sepse , Humanos , Estudos Prospectivos , Sepse/complicações , Sepse/prevenção & controle , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/prevenção & controle , Método Duplo-Cego , Sódio , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
AIMS: Sodium-glucose co-transporter 2 (SGLT2) inhibitors are used increasingly for patients with heart failure or chronic kidney disease to improve cardiac and renal outcomes. The use of these medications in patients with left ventricular assist devices (LVAD) is still limited and lacks evidence regarding the safety profile. In this study, we aimed to report our experience in treating 20 patients, supported by LVAD, with SGLT2 inhibitors. METHODS: We studied the safety profile of SGLT2 inhibitors (dapagliflozin and empagliflozin) in 20 patients (mean age 64.7â±â12.2âyears, 75% male) supported by LVAD as destination therapy. All patients have diabetes mellitus and were prescribed SGLT2 inhibitors for glycemic control. RESULTS: SGLT2 inhibitors were well tolerated with no major adverse events. Few suction events were reported in three patients without the need for pump speed adjustment. There was no change in mean arterial pressure (71.1â±â5.6 vs. 70.1â±â4.8âmmHg, P â=â0.063). Modest decline in renal function was observed in six patients within the first weeks after drug initiation. There were no events of diabetic ketoacidosis or limb amputation. CONCLUSION: SGLT2 inhibitors are safe in patients with LVAD and may potentially improve cardiovascular and renal outcomes in this special population.
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Diabetes Mellitus Tipo 2 , Coração Auxiliar , Inibidores do Transportador 2 de Sódio-Glicose , Simportadores , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Hipoglicemiantes/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Simportadores/uso terapêutico , Glucose/uso terapêutico , SódioRESUMO
OBJECTIVE: To investigate whether GRK4 regulates the phosphorylation and function of renal CCKBR. METHODS: GRK4 A142V transgenic mice were used as an animal model of enhanced GRK4 activity, and siRNA was used to silence the GRK4 gene to investigate the regulatory effect of GRK4 on CCKBR phosphorylation and function. Finally, the co-localization and co-connection of GRK4 and CCKBR in RPT cells were observed by laser confocal microscopy and immunoprecipitation to explore the mechanism of GRK4 regulating CCKBR. RESULTS: Gastrin infusion significantly increased urinary flow and sodium excretion rates in GRK4 WT mice (P < .05). GRK4 siRNA did not affect CCKBR protein expression in WKY RPT cells and SHR RPT cells, but remarkably reduced CCKBR phosphorylation in WKY and SHR RPT cells (P < .05). The inhibitory effect of gastrin on Na+-K+ -ATPase activity in WKY RPT cells was further enhanced by the reduction of GRK4 expression (P < .05), while GRK4 siRNA restored the inhibitory effect of gastrin on Na+-K+ -ATPase activity in SHR RPT cells. Laser confocal and Co-immunoprecipitation results showed that GRK4 and CCKBR co-localized in cultured RPT cells' cytoplasm. CONCLUSION: GRK4 participates in the development of hypertension by regulating the phosphorylation of renal CCKBR leading to impaired CCKBR function and water and sodium retention. Knockdown of GRK4 restored the function of CCKBR. The enhanced co-connection between GRK4 and CCKBR may be an important reason for the hyperphosphorylation of GRK4 and CCKBR involved in the pathogenesis of hypertension.
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Hipertensão , Receptor de Colecistocinina B , Animais , Camundongos , Gastrinas/farmacologia , Hipertensão/genética , RNA Interferente Pequeno , Sódio , Adenosina TrifosfatasesRESUMO
Albuminuria in kidney transplant recipients (KTRs) is associated with hypertension and aberrant glomerular filtration of serine proteases that may proteolytically activate the epithelial Na+ channel (ENaC). The present nonrandomized, pharmacodynamic intervention study aimed to investigate if inhibition of ENaC increases Na+ excretion and reduces extracellular volume in KTRs dependent on the presence of albuminuria. KTRs with and without albuminuria (albumin-to-creatinine ratio > 300 mg/g, n = 7, and <30 mg/g, n = 7, respectively) were included and ingested a diet with fixed Na+ content (150 mmol/day) for 5 days. On the last day, amiloride at 10 mg was administered twice. Body weight, 24-h urine electrolyte excretion, body water content, and ambulatory blood pressure as well as plasma renin, angiotensin II, and aldosterone concentrations were determined before and after amiloride. Amiloride led to a significant decrease in body weight, increase in 24-h urinary Na+ excretion, and decrease in 24-h urinary K+ excretion in both groups. Urine output increased in the nonalbuminuric group only. There was no change in plasma renin, aldosterone, and angiotensin II concentrations after amiloride, whereas a significant decrease in nocturnal systolic blood pressure and increase in 24-h urine aldosterone excretion was observed in albuminuric KTRs only. There was a significant correlation between 24-h urinary albumin excretion and amiloride-induced 24-h urinary Na+ excretion. In conclusion, ENaC activity contributes to Na+ and water retention in KTRs with and without albuminuria. ENaC is a relevant pharmacological target in KTRs; however, larger and long-term studies are needed to evaluate whether the magnitude of this effect depends on the presence of albuminuria.NEW & NOTEWORTHY Amiloride has a significant natriuretic effect in kidney transplant recipients (KTRs) that relates to urinary albumin excretion. The epithelial Na+ channel may be a relevant direct pharmacological target to counter Na+ retention and hypertension in KTRs. Epithelial Na+ channel blockers should be further investigated as a mean to mitigate Na+ and water retention and to potentially obtain optimal blood pressure control in KTRs.
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Hipertensão , Transplante de Rim , Desequilíbrio Hidroeletrolítico , Humanos , Amilorida/farmacologia , Amilorida/uso terapêutico , Albuminúria , Natriurese , Transplante de Rim/efeitos adversos , Renina , Aldosterona , Angiotensina II , Monitorização Ambulatorial da Pressão Arterial , Sódio/metabolismo , Redução de Peso , Peso Corporal , Água , Canais Epiteliais de SódioRESUMO
BACKGROUND: The function of macula densa nitric oxide synthase 1 (NOS1) in the regulation of renin release is controversial. This study was conducted to further elucidate the role of macula densa NOS1 in renin release and blood pressure regulation in response to salt challenges and hemorrhagic shock. METHODS: To investigate the specific role of NOS1 in the macula densa within the kidney in response to varying sodium concentrations in the diet, tissue macula densa-specific NOS1 knockout (MD-NOS1KO) and wild type (WT) mice were subjected to sequential low (0.1% NaCl) and high (1.4% NaCl) sodium diets. Separate groups of mice, consisting of both MD-NOS1KO subgroup and WT subgroup, were induced hemorrhagic shock by retro-orbital bleeding of 12 mL blood/kg body weight. Mean arterial pressure (MAP) was measured by a radio-telemetry system. Plasma renin concentration (PRC) was measured with the radioimmunoassay for both sodium diet and hemorrhagic shock experiments. RESULTS: PRCs were 371 ± 95 and 411 ± 68 ng/mL/hr in WT and MD-NOS1KO mice fed a normal sodium diet, respectively. Low salt intake stimulated an increase in the renin release by about 260% in WT mice (PRC = 1364 ± 217 ng/mL/hr, p < 0.0001) compared to the PRC under normal salt diet. However, the stimulation was significantly blunted in MD-NOS1KO mice (PRC = 678 ± 104 ng/mL/hr, p < 0.001). High salt intake suppressed the PRC to about 61% of the PRC level under a normal salt diet (p < 0.0001). Deletion of macula densa NOS1 further inhibited renin release to 33% of the levels of a normal salt diet. Hemorrhagic shock induced about a 3-fold increase in PRC in WT mice, but only about a 54% increase in the MD-NOS1KO mice (p < 0.0001). The MAP values were substantially greater in WT mice than in MD-NOS1KO mice within the first 6 hours following hemorrhagic shock (p < 0.001). Thus, WT mice showed a much quicker recovery in MAP than MD-NOS1KO mice. CONCLUSIONS: Our study demonstrated that macula densa NOS1 plays an important role in mediating renin release. This mechanism is essential in maintaining blood pressure under hypovolemic situations such as hemorrhagic shock.
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Renina , Choque Hemorrágico , Camundongos , Animais , Pressão Sanguínea , Cloreto de Sódio/farmacologia , Cloreto de Sódio na Dieta , SódioRESUMO
Introduction: Typical Western diet, rich in salt, contributes to autoimmune disease development. However, conflicting reports exist about the effect of salt on neutrophil effector functions, also in the context of arthritis. Methods: We investigated the effect of sodium chloride (NaCl) on neutrophil viability and functions in vitro, and in vivo employing the murine K/BxN-serum transfer arthritis (STA) model. Results and discussion: The effects of NaCl and external reactive oxygen species (H2O2) were further examined on osteoclasts in vitro. Hypertonic sodium-rich media caused primary/secondary cell necrosis, altered the nuclear morphology, inhibited phagocytosis, degranulation, myeloperoxidase (MPO) peroxidation activity and neutrophil extracellular trap (NET) formation, while increasing total ROS production, mitochondrial ROS production, and neutrophil elastase (NE) activity. High salt diet (HSD) aggravated arthritis by increasing inflammation, bone erosion, and osteoclast differentiation, accompanied by increased NE expression and activity. Osteoclast differentiation was decreased with 25 mM NaCl or 100 nM H2O2 addition to isotonic media. In contrast to NaCl, external H2O2 had pro-resorptive effects in vitro. We postulate that in arthritis under HSD, increased bone erosion can be attributed to an enhanced oxidative milieu maintained by infiltrating neutrophils, rather than a direct effect of NaCl.
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Artrite , Sódio , Animais , Camundongos , Cloreto de Sódio/farmacologia , Neutrófilos , Espécies Reativas de Oxigênio , Peróxido de Hidrogênio , Estresse Oxidativo , Cloreto de Sódio na DietaRESUMO
OBJECTIVES: Encephalitis, brain inflammation and swelling, most often caused by an infection or the body's immune defences, can have devastating consequences, especially if diagnosed late. We looked for clinical predictors of different types of encephalitis to help clinicians consider earlier treatment. METHODS: We conducted a multicentre prospective observational cohort study (ENCEPH-UK) of adults (> 16 years) with suspected encephalitis at 31 UK hospitals. We evaluated clinical features and investigated for infectious and autoimmune causes. RESULTS: 341 patients were enrolled between December 2012 and December 2015 and followed up for 12 months. 233 had encephalitis, of whom 65 (28%) had HSV, 38 (16%) had confirmed or probable autoimmune encephalitis, and 87 (37%) had no cause found. The median time from admission to 1st dose of aciclovir for those with HSV was 14 hours (IQR 5-50); time to 1st dose of immunosuppressant for the autoimmune group was 125 hours (IQR 45-250). Compared to non-HSV encephalitis, patients with HSV more often had fever, lower serum sodium and lacked a rash. Those with probable or confirmed autoimmune encephalitis were more likely to be female, have abnormal movements, normal serum sodium levels and a cerebrospinal fluid white cell count < 20 cells x106/L, but they were less likely to have a febrile illness. CONCLUSIONS: Initiation of treatment for autoimmune encephalitis is delayed considerably compared with HSV encephalitis. Clinical features can help identify patients with autoimmune disease and could be used to initiate earlier presumptive therapy.
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Doenças Autoimunes do Sistema Nervoso , Encefalite , Humanos , Adulto , Feminino , Masculino , Estudos Prospectivos , Encefalite/diagnóstico , Encefalite/epidemiologia , Sódio , Reino Unido/epidemiologiaRESUMO
OBJECTIVE: To determine the effects of salt reduction interventions designed for home cooks and family members. DESIGN: Cluster randomised controlled trial. SETTING: Six provinces in northern, central, and southern China from 15 October 2018 to 30 December 2019. PARTICIPANTS: 60 communities from six provinces (10 communities from each province) were randomised; each community comprised 26 people (two people from each of 13 families). INTERVENTIONS: Participants in the intervention group received 12 month interventions, including supportive environment building for salt reduction, six education sessions on salt reduction, and salt intake monitoring by seven day weighed record of salt and salty condiments. The control group did not receive any of the interventions. MAIN OUTCOME MEASURE: Difference between the two groups in change in salt intake measured by 24 hour urinary sodium during the 12 month follow-up. RESULTS: 1576 participants (775 (49.2%) men; mean age 55.8 (standard deviation 10.8) years) from 788 families (one home cook and one other adult in each family) completed the baseline assessment. After baseline assessment, 30 communities with 786 participants were allocated to the intervention group and 30 communities with 790 participants to the control group. During the trial, 157 (10%) participants were lost to follow-up, and the remaining 706 participants in the intervention group and 713 participants in the control group completed the follow-up assessment. During the 12 month follow-up, the urinary sodium excretion decreased from 4368.7 (standard deviation 1880.3) mg per 24 hours to 3977.0 (1688.8) mg per 24 hours in the intervention group and from 4418.7 (1973.7) mg per 24 hours to 4330.9 (1859.8) mg per 24 hours in the control group. Compared with the control group, adjusted mixed linear model analysis showed that the 24 hour urinary sodium excretion in the intervention group was reduced by 336.8 (95% confidence interval 127.9 to 545.7) mg per 24 hours (P=0.002); the systolic and diastolic blood pressures were reduced by 2.0 (0.4 to 3.5) (P=0.01) and 1.1 (0.1 to 2.0) mm Hg (P=0.03), respectively; and the knowledge, attitude, and behaviours in the intervention group improved significantly. CONCLUSIONS: The community based salt reduction package targeting home cooks and family members was effective in lowering salt intake and blood pressure. This intervention has the potential to be widely applied in China and other countries where home cooking remains a major source of salt intake. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800016804.
Assuntos
Família , Cloreto de Sódio na Dieta , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , China , Culinária , SódioRESUMO
IMPORTANCE: The syndrome of inappropriate antidiuresis (SIAD) can be treated with oral urea; however, compliance is impaired by its poor palatability. OBJECTIVE: To investigate whether dietary proteins could increase plasma sodium levels through urea-induced osmotic diuresis. DESIGN: An open-label, proof-of-concept trial. SETTING: University Hospital of Basel, Switzerland, between October 2021 and February 2023. PARTICIPANTS: Outpatients with chronic SIAD. INTERVENTIONS OR EXPOSURES: Ninety grams of protein daily for 7â days in the form of protein powder, followed by 30â g of oral urea daily for 7â days after a wash-out period of ≥1 week. MAIN OUTCOMES AND MEASURES: The increase in sodium levels from baseline to the end of the 7-day protein supplementation. RESULTS: Seventeen patients were included. After 7â days of 90â g daily protein supplementation (n = 17), plasma sodium levels increased from 131 (129-133) to 133 (132-137), that is, by a median of 3 mmol L-1 (0-5) (P = .01). Plasma urea levels increased by 3 mmol L-1 (1.7-4.9) (P < .01), and urine urea to creatinine ratio increased by 21.2 mmol mmol-1 (6.2-29.1) (P < .01). After 7 days of 30 g oral urea (n = 10), plasma sodium levels increased from 132 (130-133) to 134 (131-136), that is, by a median of 2 mmol L-1 (1-3) (P = .06). Plasma urea levels increased by 5.8 mmol L-1 (2.7-9.2) (P < .01), and urine urea to creatinine ratio increased by 31.0 mmol mmol-1 (18.7-45.1) (P < .01). CONCLUSIONS AND RELEVANCE: Our findings suggest that protein powder increases plasma sodium levels in patients with chronic SIAD through protein-induced ureagenesis and osmotic diuresis. The effects are comparable with oral urea.
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Hiponatremia , Síndrome de Secreção Inadequada de HAD , Humanos , Creatinina , Suplementos Nutricionais , Hiponatremia/terapia , Síndrome de Secreção Inadequada de HAD/tratamento farmacológico , Pós , Sódio , UreiaRESUMO
BACKGROUND AND OBJECTIVES: Antileucine-rich glioma-inactivated 1 (anti-LGI1) autoimmune encephalitis was first described in 2010 and is today the most common type of limbic encephalitis. During the course of the disease, 60%-88% of the patients develop hyponatremia. The etiology of the sodium disorder is unclear, often presumed to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Other electrolyte abnormalities have not been reported in association with anti-LGI1 antibody encephalitis. Due to the presence of hypomagnesemia and hypophosphatemia in our patients, we set out to try to find the expression of LGI1 protein in the kidney as an explanation for these abnormalities. METHODS: We reviewed the medical files of all patients diagnosed with anti-LGI1 antibody encephalitis, at the Department of Neurology in the Tel Aviv Medical Center between January 2011 and December 2020, exploring for electrolyte abnormalities. Using tissue staining, Western blot, mass spectrometry, and RNA expression techniques, we tried to demonstrate the expression of LGI1 protein in the human kidney. RESULTS: We identified 15 patients diagnosed with anti-LGI1 antibody encephalitis. Their average age was 65 years (44-80), and 9 were male individuals. Thirteen of the 15 patients (87%) developed varying degrees of hyponatremia. Laboratory studies demonstrated low serum osmolality, low serum blood urea nitrogen, and low uric acid, with a high urinary sodium and inappropriately high urine osmolality, supporting the presumable diagnosis of SIADH. One patient with hyponatremia that was tested, had high levels of copeptin, supporting the diagnosis of SIADH. In addition to hyponatremia, 7 patients (47%) exhibited other electrolyte abnormalities; 5 patients (33%) had overt hypophosphatemia, 4 patients (27%) had overt hypomagnesemia, and 2 other patients (13%) had borderline low magnesium levels. Western blot analysis of human kidney lysate, mass spectrometry, and qRT-PCR failed to demonstrate the expression of LGI1 protein in the kidney. DISCUSSION: Hyponatremia in patients with anti-LGI1 antibody encephalitis is due to SIADH as previously assumed. Other electrolyte abnormalities such as hypomagnesemia and hypophosphatemia occur in at least 40% of patients and may be another clue for the diagnosis of anti-LGI1 antibody encephalitis. Because we failed to demonstrate LGI1 expression in the kidney, the results of our study suggest that renal losses lead to these disturbances, most probably due to SIADH.
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Encefalite , Hiponatremia , Hipofosfatemia , Síndrome de Secreção Inadequada de HAD , Humanos , Masculino , Idoso , Feminino , Hiponatremia/diagnóstico , Hiponatremia/etiologia , Encefalite/diagnóstico , Anticorpos , Eletrólitos , SódioRESUMO
The Orthohepadnavirus genus includes hepatitis B virus (HBV) that can cause chronic hepatitis and hepatocarcinoma in humans. Recently, a novel hepadnavirus in cats, domestic cat hepadnavirus (DCH), was identified that is genetically close to HBV. DCH infection is associated with chronic hepatitis in cats, suggesting a similarity with HBV pathogenesis and the potential to use DCH as a novel animal model for HBV research. HBV is shown to use the sodium/bile acid cotransporter (NTCP) as a major cell entry receptor, but the equivalent receptor for DCH remains unknown. Here we sought to identify the entry receptor for DCH. HBV- and DCH-derived preS1 peptides efficiently bound to both human and cat NTCPs, and residue 158 of NTCP proteins determined the species-specific binding of the DCH preS1 peptide. Myrcludex B, an HBV entry inhibitor, blocked the binding of the DCH preS1 peptide. Thus, DCH and HBV may share cell entry molecules, suggesting a possibility of inter-species transmission. Furthermore, our study suggests that DCH can be useful as a novel model for HBV research.
Assuntos
Hepadnaviridae , Hepatite B , Neoplasias Hepáticas , Simportadores , Animais , Gatos , Ácidos e Sais Biliares/metabolismo , Proteínas de Transporte/metabolismo , Hepadnaviridae/metabolismo , Vírus da Hepatite B/metabolismo , Hepatite Crônica/metabolismo , Hepatócitos , Transportadores de Ânions Orgânicos Dependentes de Sódio/metabolismo , Sódio/metabolismo , Simportadores/metabolismo , Internalização do VírusRESUMO
A solitary functioning kidney (SFK) from birth predisposes to hypertension and kidney dysfunction, and this may be associated with impaired fluid and sodium homeostasis. Brief and early angiotensin-converting enzyme inhibition (ACEi) in a sheep model of SFK delays onset of kidney dysfunction. We hypothesized that modulation of the renin-angiotensin system via brief postnatal ACEi in SFK would reprogram renal sodium and water handling. Here, blood pressure (BP), kidney haemodynamics and kidney excretory function were examined in response to an isotonic saline load (0.13 ml/kg/min, 180 min) at 20 months of age in SFK (fetal unilateral nephrectomy at 100 days gestation; term 150 days), sham and SFK+ACEi sheep (ACEi in SFK 4-8 weeks of age). Basal BP was higher in SFK than sham (â¼13 mmHg), and similar between SFK and SFK+ACEi groups. Saline loading caused a small increase in BP (â¼3-4 mmHg) the first 2 h in SFK and sham sheep but not SFK+ACEi sheep. Glomerular filtration rate did not change in response to saline loading. Total sodium excretion was similar between groups. Total urine excretion was similar between SFK and sham animals but was â¼40% less in SFK+ACEi animals compared with SFK animals. In conclusion, the present study indicates that water homeostasis in response to a physiological challenge is attenuated at 20 months of age by brief early life ACEi in SFK. Further studies are required to determine if ACEi in early life in children with SFK could compromise fluid homeostasis later in life.
Assuntos
Rim Único , Animais , Ovinos , Diuréticos , Rim , Sódio , Água , Angiotensinas , Taxa de Filtração GlomerularRESUMO
Potassium humate is a widely used biostimulant known for its ability to enhance growth and improve tolerance to abiotic stress. However, the molecular mechanisms explaining its effects remain poorly understood. In this study, we investigated the mechanism of action of potassium humate using the model plant Arabidopsis thaliana. We demonstrated that a formulation of potassium humate effectively increased the fresh weight accumulation of Arabidopsis plants under normal conditions, salt stress (sodium or lithium chloride), and particularly under osmotic stress (mannitol). Interestingly, plants treated with potassium humate exhibited a reduced antioxidant response and lower proline accumulation, while maintaining photosynthetic activity under stress conditions. The observed sodium and osmotic tolerance induced by humate was not accompanied by increased potassium accumulation. Additionally, metabolomic analysis revealed that potassium humate increased maltose levels under control conditions but decreased levels of fructose. However, under stress, both maltose and glucose levels decreased, suggesting changes in starch utilization and an increase in glycolysis. Starch concentration measurements in leaves showed that plants treated with potassium humate accumulated less starch under control conditions, while under stress, they accumulated starch to levels similar to or higher than control plants. Taken together, our findings suggest that the molecular mechanism underlying the abiotic stress tolerance conferred by potassium humate involves its ability to alter starch content under normal growth conditions and under salt or osmotic stress.
Assuntos
Arabidopsis , Arabidopsis/genética , Potássio/metabolismo , Amido , Maltose/farmacologia , Estresse Fisiológico , Sódio/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Importance: Emerging evidence has consistently demonstrated that sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of heart failure (HF) hospitalization and cardiovascular (CV) death among patients with HF. However, it remains unclear how long a patient needs to live to potentially benefit from SGLT2 inhibitors in this population. Objectives: To estimate the time to benefit from SGLT2 inhibitors among patients with HF. Design, Setting, and Participants: This comparative effectiveness study systematically searched PubMed for completed randomized clinical trials about SGLT2 inhibitors and patients with HF published until September 5, 2022; 5 trials with the year of publication ranging from 2019 to 2022 were eventually included. Statistical analysis was performed from April to October 2022. Intervention: Addition of SGLT2 inhibitors or placebo to guideline-recommended therapy. Main Outcomes and Measures: The primary outcome was the time to first event of CV death or worsening HF, which was broadly comparable across the included trials. Results: Five trials consisting of 21â¯947 patients with HF (7837 [35.7%] were female; mean or median age older than 65 years within each trial) were included. SGLT2 inhibitors significantly reduced the risk of worsening HF or CV death (hazard ratio [HR], 0.77 [95% CI, 0.73-0.82]). Time to first nominal statistical significance (P < .05) was 26 days (0.86 months), and statistical significance was sustained from day 118 (3.93 months) onwards. A mean of 0.19 (95% CI, 0.12-0.35) months were needed to prevent 1 worsening HF or CV death per 500 patients with SGLT2 inhibitors (absolute risk reduction [ARR], 0.002). Likewise, 0.66 (95% CI, 0.43-1.13) months was estimated to avoid 1 event per 200 patients with SGLT2 inhibitors (ARR, 0.005), 1.74 (95% CI, 1.07-2.61) months to avoid 1 event per 100 patients (ARR, 0.010), and 4.96 (95% CI, 3.18-7.26) months to avoid 1 event per 50 patients (ARR, 0.020). Further analyses indicated a shorter time to benefit for HF hospitalization and among patients with diabetes or HF with reduced ejection fraction. Conclusions and Relevance: In this comparative effectiveness research study of estimating the time to benefit from SGLT2 inhibitors among patients with HF, a rapid clinical benefit in reducing CV death or worsening HF was found, suggesting that their use may be beneficial for most individuals with HF.
