Hipopotasemia no medicamentosa como biomarcador de nefropatía crónica temprana en adultos del sur de Honduras

Introducción: La hipopotasemia es un trastorno hidroelectrolítico frecuente, asociado a enfermedades sistémicas y multifactoriales, cuya forma aguda puede complicarse y causar la muerte, pero en su presentación crónica puede ser un marcador de nefropatía. Objetivo: Caracterizar el perfil del paciente con hipopotasemia no medicamentosa atendidos de emergencia. Métodos: Se revisaron los registros de pacientes mayores de 18 años con diagnóstico de hipopotasemia, ingresados en el hospital en el período de junio 2018 a diciembre de 2019. Se colectaron datos demográficos, antecedentes médicos y evolución postratamiento. Se comparó con 108 pacientes sin hipopotasemia atendidos en el período de estudio. Resultados: Se encontraron 87 casos con edad media de 38,5 años. El 90,8 % eran hombres menores de 50 años, de oficio agricultor (29,9 %), con historia de exposición a plaguicidas y a altas temperaturas ambientales. La mayoría de ellos no tenía historia de enfermedad cardiometabólicas o renal previa. El 48,3 % de todos los pacientes con hipopotasemia (n = 42) tenía creatinina mayor a 1,2 mg/dL y 63 % tenía hiponatremia. La hipopotasemia fue moderada en 39 % y severa en 12 %, los hombres 4,7 veces más afectados que las mujeres. Respecto al grupo sin hipopotasemia y creatinina anormal, tenían mayor frecuencia de enfermedad crónica (92,5 % versus 8 %). Conclusiones: Se encontró hipopotasemia no medicamentosa en varones agricultores, sin enfermedad crónica, pero con datos de nefropatía temprana e hiponatremia, se sugirió la posibilidad de nefropatía mesoamericana. Debe establecerse una alerta epidemiológica regional y un programa de prevención y control.

Introduction: Hypokalemia is a frequent hydroelectrolytic disorder, associated with systemic and multifactorial diseases, whose acute form can be complicated and cause death, but in its chronic presentation it can be a marker of nephropathy. Objective: To characterize the profile of the patient with non-drug hypokalemia seen in an emergency. Methods: The records of patients older than 18 years diagnosed with hypokalemia, admitted to the hospital from June 2018 to December 2019, were reviewed. Demographic data, medical history, and post-treatment evolution were collected. It was compared with 108 patients without hypokalemia seen in the same period. Results: 87 cases with mean age of 38.5 years were studied. 90.8% were men under 50 years of age, who worked as farmers (29.9%), with history of exposure to pesticides and high ambient temperatures. Most of them had no history of previous cardiometabolic or renal disease. 48.3% of all patients with hypokalemia (n = 42) had creatinine higher than 1.2 mg/dL and 63% had hyponatremia. Hypokalemia was moderate in 39% and severe in 12%, and it was found that men were affected 4.7 times more than women. Regarding the group without hypokalemia and abnormal creatinine, they had higher frequency of chronic disease (92.5% versus 8%). Conclusions: Non-drug hypokalemia was found in male farmers, without chronic disease, but with evidence of early nephropathy and hyponatremia. The possibility of Mesoamerican nephropathy was suggested. A regional epidemiological alert and a prevention and control program should be established.

Effects of cloperastine, a non-narcotic antitussive, on the expression of GIRK channels in the brain of methamphetamine-induced hyperactive mice

Objectives: Centrally-acting antitussives with inhibitory effects on G protein-coupled inwardly rectifying potassium (GIRK) channels have been shown to also inhibit methamphetamine-induced hyperactivity in mice. In this study, we examined if cloperastine, which is the most potent inhibitor of the GIRK channels among antitussives, is sensitive to the expression levels of GIRK channels in the brain of methamphetaminetreated mice. Materials and Methods: The brain tissues have been removed and the total RNA has been extracted from tissues. The mRNA levels were evaluated using semiquantitative reverse transcription-polymerase chain reaction. Results: The concentration levels of the mRNA of GIRK channels within the ventral midbrain of methamphetamine-treated mice increased as compared with that in control and cloperastine reduced an upregulation in GIRK2, one of the subunits of the GIRK channels, by the injection of methamphetamine. Conclusion: These findings suggest that cloperastine might ameliorate hyperactivity by inhibiting the GIRK channels in the brain.

High prevalence of hyperkalemia in Brazilian chronic dialysis patients and differences across geographic regions / Prevalência elevada de hipercalemia em pacientes brasileiros em diálise crônica e diferenças entre as regiões geográficas

Abstract Introduction: Hyperkalemia is a common multifactorial condition of people on chronic dialysis and is associated with mortality. We aimed to inform and discuss the prevalence of hyperkalemia in a large population of chronic dialysis patients in Brazil and its geographic regions. Methods: Prevalence of hyperkalemia (serum potassium ≥6.0 mEq/L) was assessed in the Brazilian Dialysis Survey (BDS) in July 2019, an online survey of voluntary participation in which all dialysis centers registered at the Brazilian Society of Nephrology were invited. Results: Approximately one-third (n=263 of 805) of the Brazilian dialysis clinics participated. The prevalence of hyperkalemia in the whole population was 16.1% (n=7,457 of 46,193; 95%CI=15.8-16.5%,), and varied from 12.1% in the North to 18.7% in the Northeast. Conclusion: We found a high prevalence of hyperkalemia in a large Brazilian chronic dialysis population. A nationwide investigation of risk factors, treatment options, and whether this high prevalence contributes to dialysis mortality is warranted.

Resumo Introdução: A hipercalemia é uma condição multifatorial comum em pessoas em diálise crônica e está associada à mortalidade. Nosso objetivo foi informar e discutir a prevalência de hipercalemia em uma grande população de pacientes em diálise crônica no Brasil e diferenças entre as regiões geográficas. Métodos: A prevalência de hipercalemia (potássio sérico ≥6,0 mEq/L) foi avaliada por meio do Censo Brasileiro de Diálise (CBD) em Julho de 2019, uma pesquisa online de participação voluntária na qual foram convidados todos os centros de diálise registrados na Sociedade Brasileira de Nefrologia. Resultados: Aproximadamente um terço (n=263 de 805) das clínicas de diálise brasileiras participaram. A prevalência de hipercalemia na população total foi de 16,1% (n=7.457 de 46.193; IC95%=15,8-16,5%), e variou de 12,1% no Norte a 18,7% no Nordeste. Conclusão: Encontramos uma elevada prevalência de hipercalemia em umagrande população brasileira em diálise crônica. É necessária uma investigação nacional dos fatores de risco, opções de tratamento e se esta alta prevalência contribui para a mortalidade desta população.

Effects of air exposure, time, temperature, and humidity on different serum electrolytes

Background: Pre-analytical, analytical, or post analytical variations can induce, change, or alter the tests results. Laboratory errors lead to unnecessary delays in test report and also increased costs by repeat samples which have become a pain to the patients. Aims and Objectives: The aims of this study were to determine alterations in the concentration of serum sodium (Na+), potassium (K+), and ionized calcium (Ca++) concentration with reference to air exposure, time, temperature, and humidity. Materials and Methods: Fifty samples as case and 50 samples as control were included from a normal healthy population in this study. After getting the samples, first readings were taken for case samples and were uncapped and the remaining samples were set aside capped at 24°C, 20% humidity for half an hour and followed by second reading which was taken. Results: Variation in the mean serum sodium between groups is 0.06 mEq/L (0.04%) and 0.08 mEq/L (0.07%) which is very negligible and insignificant (P > 0.05). The mean level of serum K+ in cases is 4.35 mEq/L and in controls is 4.27 mEq/L. After half an hour, the mean level of serum K+ in cases is 4.51 mEq/L and, in controls, is 4.29 mEq/L. Hence, the variation in results in cases is 0.16 mEq/L (3.68%) and in controls is 0.02 mEq/L (0.47%) which is highly significant (P < 0.05). The mean level of serum Ca++ in cases is 1.15 mmol/L and in controls is 1.17 mmol/L. After half an hour, the mean level of serum Ca++ in cases is 1.09 mmol/L and in controls is 1.16 mmol/L. Hence, the variation in results in cases is 0.06 mmol/L (5.22%) and in controls is 0.01 mmol/L (0.85%) which is highly significant (P < 0.05). Conclusion: Air exposure significantly alters the serum K+ and Ca++ level, but the alteration in serum Na+ level is not significant.

Comparison of serum calcium, serum magnesium, serum sodium and serum potassium in patients of preeclampsia and normal pregnant women-a cross-sectional study

Background: Preeclampsia is a clinical condition in which the patient is suffering from hypertension and proteinuria, which may be associated with pathological edema. There are multiple systems involved in pre-eclampsia which is the main culprit to complicate the pregnancy. In developing nations, approximately 4–18% of pregnancies are complicated by preeclampsia which is a major cause of morbidity and mortality globally. It does not affect pregnant females only, but may be life-threatening for growing fetuses too. If we consider the mortality in all pregnant females, about 10–15% of maternal deaths are due to pre-eclampsia. Aims and Objectives: The main objective of this study is to compare the serum calcium, magnesium, sodium and potassium level in preeclampsia patients and normal pregnant women. Materials and Methods: After taking written consent from the patients, randomly 50 pregnant females diagnosed by a gynecologist as suffering from preeclampsia were selected and for the control group 50 pregnant females who came for routine checkups were selected. 5 ml of blood was collected in the clot activator tube. The samples were analyzed for serum calcium, magnesium, sodium, and potassium on a fully automated biochemistry analyzer ”Erba XL 640” in HiTech, clinical biochemistry laboratory, B.J medical college, Ahmedabad. Results: The result showed a decreased level of serum calcium, magnesium, sodium, and potassium in the study group compared to the control group. The S. calcium level was (7.624 ± 0.84) and (8.52 ± 0.80) mg/dl in the study and control groups respectively. The S. magnesium level in the study and control were (1.47 ± 0.25) and (1.79 ± 0.18) mg/dl, respectively. S. sodium levels were (131.46 ± 6.96) and (139.92±7.86) mEq/L in the study and control groups, respectively. And the level of S. potassium in the study and control groups was (3.39 ± 0.52) and (3.67 ± 0.38) mEq/L, respectively. All the parameter values are significantly lower in a study group in comparison to control group patients (P < 0.001). Conclusion: From our study, we have concluded that the serum level of some parameters such as calcium, magnesium, sodium, and potassium was significantly decreased in patients suffering from preeclampsia. We can also conclude that these parameters can be used as a biomarker for the diagnosis of preeclampsia.

Simultaneous determination of 6 kinds of N-nitrosamines genotoxic impurities in losartan potassium raw material and its formulations by GC-MS/MS / 中国药房

OBJECTIVE To establish a method for simultaneous determination of the contents of 6 kinds of N-nitrosamines genotoxic impurities in losartan potassium raw material and its formulations. METHODS GC-MS/MS was adopted to determine 6 kinds of N-nitrosamines genotoxic impurities in losartan potassium raw material， Losartan potassium tablet， Losartan potassium capsule and Losartan potassium hydrochlorothiazide tablets， such as N-nitrosodimethylamine （NDMA）， N-nitrosodiethylamine （NDEA）， N-ethyl-N-nitroso-2-propanamine （NEiPA）， N-nitrosodiisopropylamine （NDiPA）， N-nitrosodipropylamine （NDPA） and N-nitrosodibutylamine （NDBA）. The separation was performed on SHIMADZU SH-L-17Sil MS capillary column by temperature- programmed GC， with injector temperature of 250 ℃ ， sample size of 1 μL， carrier gas of helium， and carrier flow rate of 1 mL/min. Electron ionization and multiple reaction monitoring （MRM） data acquisition mode were used， with an ion source temperature of 250 ℃ and solvent delay time of 3.1 min. RESULTS The separation among NDMA， NDEA， NEiPA， NDiPA， NDPA， NDBA and adjacent chromatographic peaks was good， and the separation rate was higher than 3.8； the linear ranges of them were 4.9-486.0， 4.9-488.5， 4.5-451.5， 6.8-683.5， 5.2-525.0 and 5.2-520.0 ng/mL（all r≥0.999 8）. The limits of quantitation were 4.86， 4.88， 4.52， 6.84， 5.25 and 5.20 ng/mL； the limits of detection were 0.97， 0.98， 0.90， 1.37， 1.05 and 1.04 ng/mL. RSDs of repeatability tests were 2.2%-5.6%（n＝6）， those of precision tests were 0.5%-1.4%（n＝6）， and those of stability tests were 1.5%-3.4%（n＝5）， respectively. Average recoveries of low-， medium- and high-concentration solution were 83.4%-103.0% （RSDs were 1.2%-6.3%， n＝3）， respectively. No one among the 6 kinds of N-nitrosamines genotoxic impurities was detected in both losartan potassium raw material and formulations. CONCLUSIONS The method is good in separation effect， highly accurate， sensitive and simple. It can be used in the determination of the 6 kinds of N-nitrosamines genotoxic impurities.

Remifentanil Down-regulates GIRK2 Expression in Rat Dorsal Root Ganglion and Spinal Dorsal Horn / 中山大学学报(医学科学版)

ObjectiveTo observe the changes in the expression and distribution of G protein-gated inwardly rectifying potassium channel subunit 2 （GIRK2） in the dorsal root ganglion （DRG） and spinal cord dorsal horn of rats with remifentanil-induced hyperalgesia. MethodsHyperalgesia was induced by intravenous infusion of remifentanil 4 μg/kg/min for 2 h in adult male SD rats. At 6th hour and on days 1， 3 and 5 following remifentanil treatment， we used immunofluorescence to examine the changes in the GIRK2 distribution and expression. Immunoblotting was used to detect GIRK2 expression of the total protein and membrane protein in DRG and spinal dorsal horn of rats. Behavioral testing was applied to evaluate the effect of intrathecal injection of GIRK2-specific agonist ML297 on thermal nociceptive threshold on day 1 after remifentanil infusion. Resultsmmunofluorescence results showed that GIRK2 was mainly co-localized with IB4-positive small neurons in DRG and nerve fibers in spinal dorsal horn. GIRK2 expression was significantly downregulated following remifentanil treatment. Immunoblotting results revealed that on day 1 following intravenous infusion of remifentanil， compared with those in the control group， GIRK2 expression levels of the total protein and membrane protein in DRG （0.47 ± 0.10 vs. 1.01 ± 0.17， P < 0.001； 0.47 ± 0.11 vs. 1.06 ± 0.12， P < 0.001） and spinal dorsal horn （0.52 ± 0.09 vs. 1.10 ± 0.08， P < 0.001； 0.54 ± 0.10 vs. 1.01 ± 0.13， P < 0.001） were all significantly decreased. The behavioral results showed that intrathecal ML297 effect on thermal withdrawal latency was significantly reduced following remifentanil treatment （P < 0.001）. ConclusionsRemifentanil might induce hyperalgesia via down-regulating GIRK2 expression in rat DRG and spinal cord dorsal horn.

Development and validation of a predictive model for the assessment of potassium-lowering treatment among hyperkalemia patients / 世界急诊医学杂志（英文）

@#BACKGROUND: Hyperkalemia is common among patients in emergency department and is associated with mortality. While, there is a lack of good evaluation and prediction methods for the efficacy of potassium-lowering treatment, making the drug dosage adjustment quite difficult. We aimed to develop a predictive model to provide early forecasting of treating effects for hyperkalemia patients. METHODS: Around 80% of hyperkalemia patients (n=818) were randomly selected as the training dataset and the remaining 20% (n=196) as the validating dataset. According to the serum potassium (K+) levels after the first round of potassium-lowering treatment, patients were classified into the effective and ineffective groups. Multivariate logistic regression analyses were performed to develop a prediction model. The receiver operating characteristic (ROC) curve and calibration curve analysis were used for model validation. RESULTS: In the training dataset, 429 patients had favorable effects after treatment (effective group), and 389 had poor therapeutic outcomes (ineffective group). Patients in the ineffective group had a higher percentage of renal disease (P=0.007), peripheral edema (P<0.001), oliguria (P=0.001), or higher initial serum K+ level (P<0.001). The percentage of insulin usage was higher in the effective group than in the ineffective group (P=0.005). After multivariate logistic regression analysis, we found age, peripheral edema, oliguria, history of kidney transplantation, end-stage renal disease, insulin, and initial serum K+ were all independently associated with favorable treatment effects. CONCLUSION: The predictive model could provide early forecasting of therapeutic outcomes for hyperkalemia patients after drug treatment, which could help clinicians to identify hyperkalemia patients with high risk and adjust the dosage of medication for potassium-lowering.

Determination of oxygen consumption in water by continuous flow injection analysis using potassium permanganate / 预防医学

Objective@#To establish a continuous flow injection analysis with potassium permanganate for determination of oxygen consumption in water.@*Methods@#The water samples and acid potassium permanganate working solutions were mixed using the continuous flow bubble spacing, and subjected to online heating reaction at 97 ℃. The peak height of the electrical signal of potassium permanganate was measured at the maximum absorption wavelength of 520 nm, and the standard substance, sulfuric acid concentration and potassium permanganate concentration were optimized according to the peak height of the electrical signal. The standard curve was plotted to measure the limit of detection, the limit of quantification, and spiked recovery rate of the method. The CODMn concentration was determined in 40 drinking water samples using acid potassium permanganate titration and continuous flow injection analysis using potassium permanganate, and the determination results of the two methods were compared with paired t-test.@*Results@#Glucose was selected as the standard substance, and the mixture of 17.5% sulfuric acid and 3.2 mmol/L potassium permanganate was selected as the working solution. CODMn had a good linear relationship at concentrations of 0 to 6.00 mg/L, with a correlation coefficient of 0.999 and higher, a detection limit of 0.013 mg/L and a quantitation limit of 0.043 mg/L, respectively. The spiked recovery rates were 90.00% to 105.00% in 40 drinking water samples, with relative standard deviations of 0.12% to 1.36%. The determination results of two permanganate index standard substances were all within the range of standard values. The relative errors of CODMn concentration were 1.55% to 9.26% between the continuous flow injection analysis using potassium permanganate and acid potassium permanganate titration, and there was no significant difference (t=2.023, P=0.185). @*Conclusion@#The established continuous flow injection analysis with potassium permanganate is feasible for batch determination of oxygen consumption in water.

Effects of repetitive transcranial magnetic stimulation on neuronal excitability and ion channels in hindlimb unloading mice / 生物医学工程学杂志

Weightlessness in the space environment affects astronauts' learning memory and cognitive function. Repetitive transcranial magnetic stimulation has been shown to be effective in improving cognitive dysfunction. In this study, we investigated the effects of repetitive transcranial magnetic stimulation on neural excitability and ion channels in simulated weightlessness mice from a neurophysiological perspective. Young C57 mice were divided into control, hindlimb unloading and magnetic stimulation groups. The mice in the hindlimb unloading and magnetic stimulation groups were treated with hindlimb unloading for 14 days to establish a simulated weightlessness model, while the mice in the magnetic stimulation group were subjected to 14 days of repetitive transcranial magnetic stimulation. Using isolated brain slice patch clamp experiments, the relevant indexes of action potential and the kinetic property changes of voltage-gated sodium and potassium channels were detected to analyze the excitability of neurons and their ion channel mechanisms. The results showed that the behavioral cognitive ability and neuronal excitability of the mice decreased significantly with hindlimb unloading. Repetitive transcranial magnetic stimulation could significantly improve the cognitive impairment and neuroelectrophysiological indexes of the hindlimb unloading mice. Repetitive transcranial magnetic stimulation may change the activation, inactivation and reactivation process of sodium and potassium ion channels by promoting sodium ion outflow and inhibiting potassium ion, and affect the dynamic characteristics of ion channels, so as to enhance the excitability of single neurons and improve the cognitive damage and spatial memory ability of hindlimb unloading mice.

Effect of Zhenwu Decoction on electrical remodeling of cardiomyocytes in heart failure via I_(to)/Kv channels / 中国中药杂志

This study aimed to investigate the underlying mechanism of Zhenwu Decoction in the treatment of heart failure by regulating electrical remodeling through the transient outward potassium current(I_(to))/voltage-gated potassium(Kv) channels. Five normal SD rats were intragastrically administered with Zhenwu Decoction granules to prepare drug-containing serum, and another seven normal SD rats received an equal amount of distilled water to prepare blank serum. H9c2 cardiomyocytes underwent conventional passage and were treated with angiotensin Ⅱ(AngⅡ) for 24 h. Subsequently, 2%, 4%, and 8% drug-containing serum, simvastatin(SIM), and BaCl_2 were used to interfere in H9c2 cardiomyocytes for 24 h. The cells were divided into a control group [N, 10% blank serum + 90% high-glucose DMEM(DMEM-H)], a model group(M, AngⅡ + 10% blank serum + 90% DMEM-H), a low-dose Zhenwu Decoction-containing serum group(Z1, AngⅡ + 2% drug-containing serum of Zhenwu Decoction + 8% blank serum + 90% DMEM-H), a medium-dose Zhenwu Decoction-containing serum group(Z2, AngⅡ + 4% drug-containing serum of Zhenwu Decoc-tion + 6% blank serum + 90% DMEM-H), a high-dose Zhenwu Decoction-containing serum group(Z3, AngⅡ + 8% drug-containing serum of Zhenwu Decoction + 2% blank serum + 90% DMEM-H), an inducer group(YD, AngⅡ + SIM + 10% blank serum + 90% DMEM-H), and an inhibitor group(YZ, AngⅡ + BaCl_2 + 10% blank serum + 90% DMEM-H). The content of ANP in cell extracts of each group was detected by ELISA. The relative mRNA expression levels of ANP, Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 were detected by real-time quantitative PCR. The protein expression of Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 was detected by Western blot. I_(to) was detected by the whole cell patch-clamp technique. The results showed that Zhenwu Decoction at low, medium, and high doses could effectively reduce the surface area of cardiomyocytes. Compared with the M group, the Z1, Z2, Z3, and YD groups showed decreased ANP content and mRNA level, increased protein and mRNA expression of Kv4.2, Kv4.3, DPP6, and KChIP2, and decreased protein and mRNA expression of Kv1.4, and the aforementioned changes were the most notable in the Z3 group. Compared with the N group, the Z1, Z2, and Z3 groups showed significantly increased peak current and current density of I_(to). The results indicate that Zhenwu Decoction can regulate myocardial remodeling and electrical remodeling by improving the expression trend of Kv1.4, Kv4.2, Kv4.3, KChIP2, and DPP6 proteins and inducing I_(to) to regulate Kv channels, which may be one of the mechanisms of Zhenwu Decoction in treating heart failure and related arrhythmias.

Antiarrhythmic active components in traditional Chinese medicine acting on potassium channels / 中国中药杂志

Arrhythmia is an external manifestation of cardiac electrophysiological disorder. It exists in healthy people and patients with various heart diseases, which is often associated with other cardiovascular diseases. The contraction and diastole of myocardium are inseparable from the movement of ions. There are many ion channels in the membrane and organelle membrane of myocardium. The dynamic balance of myocardial ions is vital in maintaining myocardial electrical homeostasis. Potassium ion channels that have a complex variety and a wide distribution are involved in the whole process of resting potential and action potential of cardiomyocytes. Potassium ion channels play a vital role in maintaining normal electrophysiological activity of myocardium and is one of the pathogenesis of arrhythmia. Traditional Chinese medicine(TCM)has unique advantages in treating arrhythmia for its complex active components and diverse targets. A large number of TCM preparations have definite effect on treating arrhythmia-related diseases, whose antiarrhythmic mechanism may be related to the effect on potassium channel. This article mainly reviewed the relevant studies on the active components in TCM acting on different potassium channels to provide references for clinical drug use and development.

Nutritional efficiency in sunflower cultivars under dosages of potassium in semiarid region

Potassium (K) participates in critical processes in sunflower cultivation, such as osmotic regulation and translocation of photosynthesis. However, the absorption or accumulation of this nutrient occurs differently owing to edaphoclimatic factors or between cultivars. The objective of this study was to evaluate the nutritional efficiency of sunflower cultivars as a function of different dosage K dosages in a semiarid region. To this end, two experiments were conducted in 2016 and 2017. The treatments consisted of five dosages of K at 0, 30, 60, 90, and 120 kg ha-1 K2O and four sunflower cultivars, Aguará 6, Altis 99, Multissol, and BRS 122. The experimental design was a randomized block with four replications and subdivided plots. The characteristics evaluated were agronomic efficiency, physiological efficiency, recovery efficiency, utilization efficiency, and accumulation of total K in the plant. Sunflower cultivars responded to K dosages in the two crops, with variations in efficiency parameters. Crop 2 showed better nutritional efficiency compared to crop 1. Aguará 6 showed greater nutritional efficiency than the other two crops. The use of dosages between 75 and 91 kg ha-1 of K2O provided better efficiency in K usage for the cultivars.

Control of sodium and potassium homeostasis by renal distal convoluted tubules

Distal convoluted tubules (DCT), which contain the Na-Cl cotransporter (NCC) inhibited by thiazide diuretics, undergo complex modulation to preserve Na+ and K+ homeostasis. The lysine kinases 1 and 4 (WNK1 and WNK4), identified as hyperactive in the hereditary disease pseudohypoaldosteronism type 2, are responsible for activation of NCC and consequent hypokalemia and hypertension. WNK4, highly expressed in DCT, activates the SPAK/OSR1 kinases, which phosphorylate NCC and other regulatory proteins and transporters in the distal nephron. WNK4 works as a chloride sensor through a Cl- binding site, which acts as an on/off switch at this kinase in response to changes of basolateral membrane electrical potential, the driving force of cellular Cl- efflux. High intracellular Cl- in hyperkalemia decreases NCC phosphorylation and low intracellular Cl- in hypokalemia increases NCC phosphorylation and activity, which makes plasma K+ concentration a central modulator of NCC and of K+ secretion. The WNK4 phosphorylation by cSrc or SGK1, activated by angiotensin II or aldosterone, respectively, is another relevant mechanism of NCC, ENaC, and ROMK modulation in states such as volume reduction, hyperkalemia, and hypokalemia. Loss of NCC function induces upregulation of electroneutral NaCl reabsorption by type B intercalated cells through the combined activity of pendrin and NDCBE, as demonstrated in double knockout mice (KO) animal models, Ncc/pendrin or Ncc/NDCBE. The analysis of ks-Nedd-4-2 KO animal models introduced the modulation of NEDD4-2 by intracellular Mg2+ activity as an important regulator of NCC, explaining the thiazide-induced persistent hypokalemia.

Development of microparticles and microparticulated tablets containing piperine

Abstract Piper nigrum (black pepper) is used in Indian traditional medicine and its main alkaloid, Piperine (PIP), presents antioxidant, antitumor and neuroprotective pharmacological properties. This substance is insoluble in aqueous media and can irritate the gastrointestinal tract. Aiming to avoid these inconvenient characteristics and enable PIP oral administration, this study suggested the PIP microencapsulation through the emulsion-solvent evaporation method and the preparation of microparticulated tablets by direct compression. An UV-spectroscopy method was validated to quantify PIP. Microparticles and microparticulated tablets were successfully obtained and the microparticles exhibited excellent flow. The scanning electron microscopy images showed that PIP microparticles were intact after compression. The in vitro release showed a controlled release of PIP from microparticles and PIP microparticles from tablets in comparison to PIP and PIP tablets. The release profiles of PIP microparticles and the microparticulated tablets were similar. Therefore, tablets containing PIP microparticles are promising multiparticulated dosage forms because a tablet allows microparticles administration and the intact ones promote a controlled release, decreasing its irritating potential on the mucosa.

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.

Effect and safety of Liqing granules in assisting to reduce serum uric acid in rats / 上海预防医学

ObjectiveTo establish a rat model of hyperuricemia （HUA）， to study the effect of Liqing granules on lowering serum uric acid， and to evaluate its safety . MethodsMale SD rats were randomly divided into solvent control group and model group according to their body weight. For the model group， serum uric acid （SUA） was determined after 7 days of intra-gastric administration of potassium oxyazinate. The model group were randomly divided into model control group， positive control group， and low， medium， high dose group based on SUA level. Each group from the model group continued to receive potassium oxyazinate in the morning. The animals in the model groups received 0.5% CMC-Na， 10 mg·kg-1 benzbromarone （Doses by body weight） and Liqing granules 0.6， 1.2， 2.4 g·kg-1 （Doses by body weight）， respectively in the afternoon. 0.5% CMC-Na suspension with the same volume was given both in the morning and afternoon for the solvent control group. Levels of SUA， creatinine （CREA）， alanine aminotransferase （ALT） and aspartate transaminase （AST） were determined after 32 and 45 days administration of the test substance. ResultsSUA of the model group was （218±23） μmol·L-1 after 7 days of modeling， which was significantly higher than that of the solvent control group （P<0.001）. After 32 days administration of the test substance， SUA didn’t significantly decrease in each dose group （P>0.05）. CREA in the medium and high dose groups significantly decreased （P<0.05）. After 45 days administration of the test substance， SUA in each dose group was significantly decreased （P<0.001）， but CREA， ALT， and AST were not significantly different in each dose group in comparison with the model control group （P>0.05）. ConclusionLiqing granules can assist in lowering blood serum uric acid in the rat HUA model， and no damage to liver and kidney function is found.

Associations of genetic variants in M3 receptor with blood pressure responses to salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 M3 muscarinic acetylcholine receptor(M3 receptor), encoded by CHRM3 gene, is widely distributed in the cardiovascular system and plays an important role in cardiac regulation. The aim of this study was to assess the association of genetic variants in M3 receptor with blood pressure(BP) responses to controlled dietary sodium and potassium interventions. 【Methods】 A total of 333 subjects from 124 families were recruited from the rural areas of northern China. After a three-day baseline observation, they were sequentially on a seven-day low-salt diet, a seven-day high-salt diet, and a seven-day high-salt diet plus potassium supplementation. Thirteen CHRM3 single nucleotide polymorphisms(SNPs) were selected for analysis. 【Results】 SNP rs10802811 of the CHRM3 was significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to both low-salt and high-salt diets while SNPs rs6429147, rs373288072, rs114677844 and rs663148 showed significant associations with systolic BP(SBP) and MAP responses to high-salt diet. In addition, SNP rs6692904 was significantly associated with SBP, DBP and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in M3 receptor are significantly associated with BP responses to sodium and potassium intervention, suggesting that M3 receptor may be mechanistically involved in BP salt and potassium sensitivity.

Association of genetic variants in uromodulin with blood pressure responses to dietary salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 Based on our previously established salt-sensitive hypertension cohort, we aimed to examine the association of genetic variants in uromodulin with blood pressure(BP) responses to dietary interventions of sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Mei County, Shaanxi Province, were recruited to establish the salt-sensitive hypertension study cohort. Among them, 333 non-parent subjects were selected and sequentially maintained on a normal-diet for 3 days, low-salt diet for 7 days, then a high-salt diet for 7 days and a high-salt diet with potassium supplementation for another 7 days. Thirteen single nucleotide polymorphisms(SNPs) in the uromodulin gene were genotyped on the MassARRAY platform. 【Results】 BP levels decreased from the baseline to low-salt diet, increased from low-salt to high-salt diet, and decreased again from the high-salt diet to the high-salt plus potassium supplementation intervention. SNPs rs77875418 and rs4997081 of the uromodulin gene were significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to high-salt diet. In addition, SNPs rs77875418, rs79245268, rs4293393, rs6497476, rs4997081, rs13333226, and rs12917707 were significantly associated with systolic BP(SBP), DBP, and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in uromodulin gene are significantly associated with BP responses to sodium and potassium supplementation, suggesting that uromodulin may be mechanistically involved in BP sodium-sensitivity and potassium-sensitivity.