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.

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.

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.

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

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

Leptospiral c-di-AMP-binding protein regulates potassium ion transport / 中华微生物学和免疫学杂志

Objective:To investigate whether KtrA was a binding protein of c-di-AMP, the second messenger in Leptospira, and to explore the function and regulatory mechanism of the c-di-AMP-KtrA/B system. Methods:KtrA gene was amplified by PCR and cloned into pET42a plasmid to construct the pET42a ktrA prokaryotic expression vector. Then the vector was transferred into E. coli BL21DE3 to construct an engineering bacterium E. coli BL21DE3 pET42a-ktrA for the expression of recombinant KtrA (rKtrA). The expressed rKtrA was purified by affinity chromatography. BIAcore technology was used to detect the binding ability of rKtrA to c-di-AMP. Bacterial two-hybrid analysis was used to analyze the interaction between KtrA and KtrB in the leptospiral Ktr system with or without exogenetic c-di-AMP. The above genes were then complemented into the potassium transport-deficient E. coli mutants to analyze the function of the c-di-AMP-KtrA/B pathway. Results:An prokaryotic engineering bacterium for the expression of ktrA gene of Leptospira was constructed successfully. The purified rKtrA could specifically bind to c-di-AMP. There was interaction between KtrA and KtrB, but the interaction could be dissociated by c-di-AMP. The KtrA/B system was involved in potassium ion uptake and it was negatively regulated by c-di-AMP. Conclusions:Leptospiral KtrA was a c-di-AMP-binding protein and the c-di-AMP-KtrA/B system was involved in potassium ion transport.

Research progress in changes of Na + concentration and Na +/K + value in breast milk of lactating women at different conditions / 中华围产医学杂志

Breastfeeding is a key factor influencing infants' short- and long-term health, thus making it important to monitor breast function. This article reviews the changes in Na + concentration and Na +/K + value in breast milk during secretory activation and at physiological and pathological conditions, aiming to provide a reference for early clinical assessment and intervention of physiological or pathological changes in the breast during lactation and to improve the outcome of breastfeeding.

Voltage-gated potassium channel-complex antibodies associated clinical syndromes with myasthenia gravis complicated with thymoma: analysis of 2 cases and literature review / 中华神经科杂志

Objective:To investigate the clinical characteristics and outcome of patients with voltage-gated potassium channel complex (VGKCc) antibody associated clinical syndromes complicated with myasthenia gravis (MG) with thymoma.Methods:The clinical history, examinations and follow-up prognosis of 2 cases of VGKCc antibodies associated clinical syndromes with MG complicated with thymoma in Qilu Hospital (Qingdao), Cheeloo College of Medicine,Shandong University in September 2020 and December 2020 were reviewed. Related literatures were summarized at the same time.Results:Case 1, a 64-year-old female clinically presented with cognitive impairment, psychosis, and epilepsy seizures, whose serum autoimmune antibody testing showed positive leucine-rich glioma-inhibited 1 (LGI1) antibody, was diagnosed as anti-LGI1 encephalitis,and had history of MG with thymoma. Her symptoms were improved by immunotherapy. Case 2, a 67-year-old male, was diagnosed as MG, and developed cognitive impairment, myokymia and autonomic dysfunction later. His serum autoimmune antibody testing showed positive contactin associated protein-like 2 antibody. Therefore, Morvan syndrome complicated with MG with thymoma was definitely diagnosed. After admission, the patient was improved with immunotherapy and thymoma resection.Conclusions:Patients with VGKCc antibody-associated clinical syndromes complicated with MG have the clinical characteristics of the two diseases simultaneously, and there is also crossover. Immunotherapy and treatment for thymoma are generally effective.

Effect of different immersion bath methods on the healing of skin lesions in patients with pemphigus / 中华皮肤科杂志

Objective:To analyze effects of ozone bath, 1∶8 000 potassium permanganate bath and 1∶5 000 potassium permanganate bath on the recovery of skin lesions in patients with pemphigus.Methods:Patients with pemphigus, who received immersion bath treatment during their hospitalization, were retrospectively collected from Department of Dermatology, Peking University First Hospital from January 2016 to June 2021. The efficacy and safety of different immersion bath methods including ozone bath, 1∶8 000 potassium permanganate bath and 1∶5 000 potassium permanganate bath were compared. Categorical variables were compared using chi-square test or Fisher′s exact test, and univariate and multivariate logistic regression models were used to analyze relationships between candidate variables and patients′ condition at discharge.Results:A total of 74 patients with pemphigus were included, including 45 (60.81%) males and 29 (39.19%) females, their age ( M[ Q1, Q3]) was 52 (41, 60) years, and the median percentage of primary skin lesion area in body surface area was 40%. There were no significant differences in hospital stays, disease duration (time from onset to admission) , gender ratio or skin lesion areas among patients receiving ozone bath (32 cases) , patients receiving 1∶8 000 potassium permanganate bath (25 cases) and those receiving 1∶5 000 potassium permanganate bath (17 cases, all P > 0.05) . These patients still received other treatments, including glucocorticoids, gamma globulin, plasma transfusion, rituximab, immunosuppressants, topical antibiotics, etc., and there was no significant difference in the proportions of patients using the above therapies among the three groups (all P > 0.05) , while the ozone bath group showed a lower proportion of patients using systemic antibiotics compared with the two potassium permanganate bath groups (both P < 0.01) . At discharge, in the ozone bath group, 1 case was improved, 21 were nearly cured, and 10 were cured; in the 1∶8 000 potassium permanganate bath group, 4 cases were improved, 13 were nearly cured, and 8 were cured; in the 1∶5 000 potassium permanganate bath group, 5 were improved, 8 were nearly cured, and 4 were cured. The proportion of well-recovered patients was significantly higher in the ozone bath group (31/32 cases) than in the potassium permanganate bath group (33/42 cases, P = 0.036) . Univariate and multivariate analyses showed that ozone bath significantly affected the patients′ condition at discharge ( P < 0.05) , and was an independent predictor of "good recovery" at discharge ( HR = 8.455, 95% CI: 1.011 - 70.672, P = 0.049) . Conclusion:Ozone bath therapy can facilitate recovery of skin lesions in patients with pemphigus.

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.

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.

Association of genetic variants in NEDD4L with blood pressure responses to dietary salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 4-like protein with down-regulated expression and development in neural precursor cells (NEDD4L) plays an important role in blood pressure (BP) regulation and sodium homeostasis by regulating epithelial sodium channel protein. In this study, we aimed to explore the relationship of NEDD4L gene polymorphisms with BP responses to sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Meixian County, Shaanxi Province, were recruited to establish a salt-sensitive hypertension study cohort. All the subjects received a 3-day baseline survey, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Their BP was measured and peripheral blood samples were collected at different intervention periods. The 14 gene polymorphisms of NEDD4L gene were genotyped and analyzed by MassARRAY platform. 【Results】 BP decreased on a low-salt diet, and significantly increased on a high-salt diet, and decreased again after potassium supplementation. NEDD4L SNPs rs74408486 were significantly associated with systolic BP, diastolic BP and mean arterial pressure responses to the low-salt diet. SNPs rs292449 and rs2288775 were significantly associated with pulse pressure response to the high-salt diet. In addition, SNPs rs563283 and rs292449 were significantly associated with diastolic BP, mean arterial pressure, and pulse pressure responses to high-salt and potassium supplementation diet. 【Conclusion】 NEDD4L gene polymorphisms were significantly associated with BP responses to sodium and potassium intake, suggesting that NEDD4L gene may be involved in the development of salt sensitivity and potassium sensitivity.

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

【Objective】 Corin, a transmembrane serine protease that can cleave atrial natriuretic peptide precursor (pro-ANP) into atrial natriuretic peptide with smaller bioactive molecules, participates in the pathophysiological process of hypertension and cardiac hypertrophy. The purpose of this study was to explore the relationship of Corin gene variation with blood pressure responses to sodium and potassium dietary interventions. 【Methods】 In 2004, we recruited 514 participants from 124 families in 7 villages of Baoji, Shaanxi Province, China. All the subjects received a 3-day normal diet, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Fifteen single nucleotide polymorphisms (SNPs) of Corin gene were selected for final analysis. 【Results】 SNPs rs12509275 were significantly associated with diastolic blood pressure (DBP) response to low-salt diet, while rs3749584 was associated with pulse pressure (PP) response to low-salt diet.SNP rs3749584 and rs10517195 were significantly associated with PP response to high-salt diet. In addition,rs17654278 were significantly associated with systolic blood pressure (SBP) response to high-salt and potassium supplementation, rs2271037 was significantly correlated with DBP responses to high-salt and potassium supplementation, and rs4695253, rs12509275, rs2351783, rs36090894 were significantly associated with PP response to high-salt and potassium supplementation. 【Conclusion】 Corin gene polymorphisms were associated with blood pressure response to sodium and potassium, suggesting that Corin gene may be involved in pathophysiological process of salt sensitivity and potassium sensitivity.

Alterations in dendritic length and branch and K / 解剖学报

Objective To study the morphology of olfactory bulb(OB) neurons and the change of related proteins, and explore the causes of olfactory dysfuction in Alzheimer' s disease(AD). Methods Golgi-Cox staining technique was used to evaluate the morphological changes of neurons in the OB and anterior piriform cortex (aPC) of APP/PS1 AD model mice. The morphology of neurons was determined by Sholl analysis. Western blotting was used to evaluate the levels of protein expression. Results The results of Golgi-Cox showed that the dendrite length and branch number reduced significantly in the OB neurons of 3-5-month-old APP/PS1 mice, an age that the mice did not show the pathological characteristics and cognitive impairment of AD. Western blotting analysis showed that levels of potassium chloride cotransporter 2(KCC2), a potassium chloride transporter crucial for neuronal morphology and synaptic function, decreased significantly in the OB of 3-5-month-old APP/PS1 mice. Conclusion Abnormal neuronal morphology and KCC2 signal might be the basis of early olfactory dysfunction in AD. Thus, maintaining normal KCC2 signal may be one of the keys to intervene the olfactory abnormalities in the early stage of AD.