MiR-21-5p alleviates trigeminal neuralgia in rats through down-regulation of voltage-gated potassium channel Kv1.1 / 中南大学学报(医学版)

Objective:Trigeminal neuralgia(TN)is a common neuropathic pain.Voltage-gated potassium channel(Kv)has been confirmed to be involved in the occurrence and development of TN,but the specific mechanism is still unclear.MicroRNA may be involved in neuropathic pain by regulating the expression of Kv channels and neuronal excitability in trigeminal ganglion(TG).This study aims to explore the relationship between Kv1.1 and miR-21-5p in TG with a TN model,evaluate whether miR-21-5p has a regulatory effect on Kv1.1,and to provide a new target and experimental basis for the treatment of TN. Methods:A total of 48 SD rats were randomly divided into 6 groups:1)a sham group(n= 12),the rats were only sutured at the surgical incision without nerve ligation;2)a sham+ agomir NC group(n=6),the sham rats were microinjected with agomir NC through stereotactic brain injection in the surgical side of TG;3)a sham+miR-21-5p agomir group(n=6),the sham rats were microinjected with miR-21-5p agomir via stereotactic brain injection in the surgical side of TG;4)a TN group(n=12),a TN rat model was constructed using the chronic constriction injury of the distal infraorbital nerve(dIoN-CCI)method with chromium intestinal thread;5)a TN+antagonist NC group(n=6),TN rats were microinjected with antagonist NC through stereotactic brain injection method in the surgical side of TG;6)a TN+miR-21-5p antagonist group(n=6),TN rats were microinjected with miR-21-5p antagonist through stereotactic brain injection in the surgical side of TG.The change of mechanical pain threshold in rats of each group after surgery was detected.The expressions of Kv1.1 and miR-21-5p in the operative TG of rats were detected by Western blotting and real-time reverse transcription polymerase chain reaction.Dual luciferase reporter genes were used to determine whether there was a target relationship between Kv1.1 and miR-21-5p and whether miR-21-5p directly affected the 3'-UTR terminal of KCNA1.The effect of brain stereotaxic injection was evaluated by immunofluorescence assay,and then the analogue of miR-21-5p(agomir)and agomir NC were injected into the TG of rats in the sham group by brain stereotaxic apparatus to overexpress miR-21-5p.The miR-21-5p inhibitor(antagomir)and antagomir NC were injected into TG of rats in the TN group to inhibit the expression of miR-21-5p.The behavioral changes of rats before and after administration were observed,and the expression changes of miR-21-5p and Kv1.1 in TG of rats after intervention were detected. Results:Compared with the baseline pain threshold,the facial mechanical pain threshold of rats in the TN group was significantly decreased from the 5th to 15th day after the surgery(P<0.05),and the facial mechanical pain threshold of rats in the sham group was stable at the normal level,which proved that the dIoN-CCI model was successfully constructed.Compared with the sham group,the expression of Kv1.1 mRNA and protein in TG of the TN group was down-regulated(both P<0.05),and the expression of miR-21-5p was up-regulated(P<0.05).The results of dual luciferase report showed that the luciferase activity of rno-miR-21-5p mimics and KCNA1 WT transfected with 6 nmol/L or 20 nmol/L were significantly decreased compared with those transfected with mimic NC and wild-type KCNA1 WT,respectively(P<0.001).Compared with low dose rno-miR-21-5p mimics(6 nmol/L)co-transfection group,the relative activity of luciferase in the high dose rno-miR-21-5p mimics(20 nmol/L)cotransfection group was significantly decreased(P<0.001).The results of immunofluorescence showed that drugs were accurately injected into TG through stereotaxic brain.After the expression of miR-21-5p in the TN group,the mechanical pain threshold and the expression of Kv1.1 mRNA and protein in TG were increased.After overexpression of miR-21-5p in the sham group,the mechanical pain threshold and the expression of Kv1.1 mRNA and protein in TG were decreased. Conclusion:Both Kv1.1 and miR-21-5p are involved in TN and miR-21-5p can regulate Kv1.1 expression by binding to the 3'-UTR of KCNA1.

Clinical efficacy of pyrimidolast potassium combined with praprofen in the treatment of allergic conjunctivitis / 基础医学与临床

Objective To investigate the clinical effect of pyrimidolast potassium combined with praprofen eye drops in the treatment of allergic conjunctivitis(AC).Methods From March 2021 to March 2023,186 patients with AC were selected from Beijing Gulou Hospital of Traditional Chinese Medicine.The patients were randomly assigned to a observation group and a control group with 93 in each.Pyrimidolast potassium eye drops(1-2 drops,b.i.d,)was given to both groups,and praprofen eye drops(1-2 drops,q.i.d)was given only to the observation group.Both groups of patients were treated for 14 days.Clinical symptoms,signs scores,tear film stability and corneal epitheli-um injury were compared between the two groups.Results After treatment,the total effective rate of observation group(93.54%)was higher than that of control group(80.65%).Symptom scores in observation group and control group were 0.19±0.66 and 0.70±0.69,respectively.The scores of physical signs were 0.09±0.51 and 0.42±0.40,respectively.Tear film stability was 10.81±2.58 and 9.39±1.87,respectively.The injury of corneal epithelium was 0.98±0.46 and 2.05±0.90,respectively,and the difference was statistically significant(P＜0.05).Conclusions Compared with the patients treated with pyriferast potassium eye drops only,the combined applica-tion of pralprofen eye drops can synergically enhance the efficacy of drugs,improve the symptoms and signs of patients,effectively repair corneal injury and stabilize tear film.

Association of gene polymorphisms in microRNA with blood pressure responses to salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 To investigate the relationship of miRNA gene polymorphisms with blood pressure (BP) responses to the sodium and potassium diet intervention. 【Methods】 In 2004, we recruited 514 participants from 124 families in seven villages of Baoji, Shaanxi Province, China. All subjects were given a three-day normal diet, followed by a seven-day low-salt diet, a seven-day high-salt diet, and finally a seven-day high-salt and potassium supplementation. A total of 19 miRNA single nucleotide polymorphisms (SNPs) were selected for analysis. 【Results】 Throughout the sodium-potassium dietary intervention, the BP of the subjects fluctuated across all phases, showing a decrease during the low-salt period and an increase during the high-salt period, followed by a reduction in BP subsequent to potassium supplementation during the high-salt diet. MiR-210-3p SNP rs12364149 was significantly associated with systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) responses to low-salt diet. MiR-4638-3p SNP rs6601178 was significantly associated with SBP while miR-26b-3p SNP rs115254818 was significantly associated with MAP responses to low-salt intervention. In addition, miR-26b-3p SNP rs115254818 was significantly correlated with SBP, DBP and MAP responses to high-salt intervention. MiR-1307-5p SNPs rs11191676 and rs2292807 were associated with SBP and MAP responses to high-salt diet. MiR-4638-3p SNP rs6601178, miR-210-3p SNP rs12364149, miR-382-5p SNP rs4906032 and rs4143957 were significantly associated with SBP response to high-salt diet. In addition, miR-26b-3p SNP rs115254818 was significantly associated with SBP, DBP and MAP responses to potassium supplementation. MiR-1307-5p SNPs rs11191676, rs2292807, and miR-19a-3p SNP rs4284505 were significantly associated with SBP responses to high-salt and potassium supplementation. 【Conclusion】 miRNA gene polymorphisms are associated with BP response to sodium and potassium, suggesting that miRNA genes may be involved in the pathophysiological process of salt sensitivity and potassium sensitivity.

Associations of genetic variants in GLP-1R with blood pressure responses to dietary sodium and potassium interventions / 西安交通大学学报(医学版)

【Objective】 To investigate the association between genetic variations in the glucagon-like peptide-1 receptor (GLP-1R) gene and BP responses to sodium and potassium intake. 【Methods】 A total of 514 subjects from 124 families were recruited in Meixian County, Shaanxi Province, in 2004, resulting in the establishment of a "salt-sensitive hypertension study cohort" . The subjects followed a dietary regimen which involved a normal diet for 3 days, a low-salt diet for 7 days, a high-salt diet for 7 days, and a high-salt potassium-supplemented diet for 7 days. BP measurement was conducted at different intervention periods, and peripheral blood samples were collected. Additionally, eight single nucleotide polymorphisms (SNPs) of the GLP-1R gene were genotyped using the MassARRAY detection platform. 【Results】 The GLP-1R gene SNP rs9462472 exhibited a significant association with systolic BP, diastolic BP, and mean arterial pressure response to high-salt intervention. Similarly, SNP rs2268637 showed a significant association with systolic BP response to high-salt intervention. Furthermore, SNP rs2268637 was significantly associated with systolic BP and mean arterial pressure responses to high-salt plus potassium supplementation intervention. 【Conclusion】 Our findings indicate a significant association of genetic variations in the GLP-1R gene with BP responses to sodium and potassium intake. This suggests that the GLP-1R gene plays a role in the regulation of BP salt sensitivity and potassium sensitivity.

Potassium dehydroandrographolide succinate regulates the MyD88/CDH13 signaling pathway to enhance vascular injury-induced pathological vascular remodeling / 中国天然药物

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.

Progress on pharmaceutical characteristics of potassium-competitive acid blocker / 药学实践与服务

As a new class of acid inhibitors, potassium-competitive acid blocker（P-CAB） inhibits the conformational transition of H+, K+-ATPase with subsequent suppression of H+, K+ exchanging by binding reversibly near the K+ binding site of H+, K+-ATPase, which results in the inhibition of gastric acid secretion in a K+-competitive manner. The unique structure and novel mechanism of P-CAB contribute to the pharmaceutical characteristics superior to other PPIs, making it a new alternative for acid-related diseases（ARDs）. Progress on pharmaceutical characteristics of P-CAB were reviewed in this paper.

Effects of sacubitril/valsartan on renal function in patients with primary hypertension / 中国药房

OBJECTIVE To investigate the effects of sacubitril/valsartan on renal function in patients with primary hypertension. METHODS A retrospective study was conducted among patients with primary hypertension who were admitted to PLA Strategic Support Force Characteristic Medical Center from January 2018 to June 2023. Based on their medication， they were divided into two groups： sacubitril/valsartan group and valsartan group. Propensity score matching was used to match baseline data between the two groups. Patients were treated with antihypertensive drugs based on improving their lifestyle. Sacubitril/valsartan group additionally received oral administration of 200 mg Sacubitril/valsartan tablets once daily， while valsartan group additionally received oral administration of 80 mg Valsartan capsules once daily. The increase amplitude of serum creatinine from baseline， the proportion of patients with elevated serum creatinine ＞30%-50% or ＞50%， and the proportion of patients with hyperkalemia （serum potassium ≥5.5 mmol/L） were compared between two groups at 2 months and 6 months after treatment. The trends of changes in serum creatinine， serum potassium and estimated glomerular filtration rate （eGFR） were compared between the two groups before treatment （at baseline）， 2 months and 6 months after treatment. RESULTS After propensity score matching， there were 62 patients in sacubitril/valsartan group and 61 patients in valsartan group； there were no significant differences in baseline characteristics between the two groups before treatment （P＞0.05）， indicating comparability. After 6 months of treatment， the increase of serum creatinine in the sacubitril/valsartan group was significantly lower than that in the valsartan group （P＝0.003）； the proportion of patients with elevated serum creatinine ＞30%-50% in the sacubitril/valsartan group was significantly lower than that in the valsartan group （P＝0.045）. None of the patients experienced hyperkalemia events after 2 months and 6 months of treatment. Repeated measures analysis of variance showed significantly statistical differences in serum creatinine and eGFR between the two groups within 6 months of treatment （P＜0.001）. Patients taking valsartan experienced a continuous increase in serum creatinine levels and a decrease in eGFR， while patients taking sacubitril/valsartan showed a first increase and then a decrease in serum creatinine levels， and a first decrease and then an increase in eGFR with a prolonged duration of medication. CONCLUSIONS Sacubitril/valsartan can delay or even reverse the decline in renal function levels， and limit the deterioration of renal function in patients with primary hypertension， without increasing the risk of hyperkalemia.

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.

Hipopotasemia no medicamentosa como biomarcador de nefropatía crónica temprana en adultos del sur de Honduras / Non-drug Hypokalemia as Biomarker of Early Chronic Kidney Disease in Adults from Southern 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 por ciento eran hombres menores de 50 años, de oficio agricultor (29,9 por ciento), 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 por ciento de todos los pacientes con hipopotasemia (n = 42) tenía creatinina mayor a 1,2 mg/dL y 63 por ciento tenía hiponatremia. La hipopotasemia fue moderada en 39 por ciento y severa en 12 por ciento, 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 por ciento versus 8 por ciento). 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(AU)

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 (29.9percent), with history of exposure to pesticides and high ambient temperatures. Most of them had no history of previous cardiometabolic or renal disease. 48.3percent of all patients with hypokalemia (n = 42) had creatinine higher than 1.2 mg/dL and 63percent had hyponatremia. Hypokalemia was moderate in 39% and severe in 12percent, 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 (92.5percent versus 8percent). 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(AU)

Alimentación basada en plantas en pacientes pediátricos: aporte de potasio y su rol en la enfermedad renal crónica / Plant-based diet in pediatric patients: potassium dietary intake and its role in chronic kidney disease

Resumen Introducción: la enfermedad renal crónica (ERC) se asocia a complicaciones como la hiperpotasemia, que pueden afectar la calidad de vida de los niños que la padecen. Así la alimentación basada en plantas (ABP) cobra relevancia ya que muchos de los alimentos incluidos son fuentes de potasio (K) entre ellos: vegetales, frutas y legumbres. Sin embargo, realizar restricciones severas en estos grupos, podría asociarse a déficits nutricionales que pongan en riesgo el crecimiento y desarrollo de niños con ERC. Objetivos: describir el rol de la ABP y su aporte de K en el abordaje nutricional de pacientes pediátricos con ERC. Materiales y método: se realizó una revisión narrativa de artículos científicos publicados desde el año 2013 a 2023, utilizando las bases de datos: PUBMED, Scielo y el buscador Google Académico. Resultados: la ABP se asocia a beneficios como disminuir la progresión de la ERC, ser precursora de compuestos alcalinos, mejorar el tránsito y la microbiota intestinal. La ingesta de K a través de la ABP no tendría una relación directa con su concentración sérica. Sin embargo, se sugiere disminuir el consumo de productos ultraprocesados y considerar los factores no alimentarios que inciden en la potasemia, como primera medida. Clasificar los alimentos según la relación k/fibra permitiría incluir una mayor variedad. Los resultados referidos a las pérdidas de K por lixiviación no son concluyentes. Conclusiones: el abordaje nutricional de la ERC a través de una ABP tendría un impacto positivo que permitiría mejorar el control de la patología y disminuir la aparición de sus complicaciones. Se destaca el rol del Lic. en Nutrición en el asesoramiento respecto a la incorporación de alimentos según el perfil de nutrientes aportados, las características de sus componentes y su impacto en el metabolismo.

Abstract Introduction: chronic kidney disease (CKD) is associated with complications such as hyperkalemia, which can affect the quality of life of children who suffer from it. Thus, the plant-based diet (PBD) becomes relevant since many of the foods included are sources of potassium (K) such as vegetables, fruits and legumes. However, severe restrictions in these groups could be associated with nutritional deficits that jeopardize the growth and development of children with CKD. Objectives: to describe the role of PBD and its contribution of K in the dietary management of pediatric patients with CKD. Materials and method: a narrative review of scientific articles published from 2013 to 2023 was carried out, using the databases: PUBMED, Scielo and the Google Scholar search engine. Results: PBD is associated with benefits such as slowing the progression of CKD, being a precursor of alkaline compounds, improving transit and intestinal microbiota. The intake of K through PBD would not have a direct relationship with its serum concentration. However, it is suggested to reduce the consumption of ultra-processed products and consider the non-food factors that affect potassium, as a first measure. Classifying foods according to the k/fiber ratio would allow for greater variety. The results regarding K leaching losses are inconclusive. Conclusions: the nutritional approach to CKD through a PBD would have a positive impact that would improve the control of the pathology and reduce the appearance of its complications. The role of the nutritionist in advising on the incorporation of foods according to the profile of nutrients provided, the characteristics of their components and their impact on metabolism is highlighted.

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.

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.

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.

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.

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.