Advances in Medical Treatment of Primary Aldosteronism / 中国医学科学杂志(英文版)

Primary aldosteronism (PA) is the most common form of secondary hypertension, with its main manifestations including hypertension and hypokalemia. Early identification of PA is extremely important as PA patients can easily develop cardiovascular complications such as atrial fibrillation, stroke, and myocardial infarction. The past decade has witnessed the rapid advances in the genetics of PA, which has shed new light on PA treatment. While surgery is the first choice for unilateral diseases, bilateral lesions can be treated with mineralocorticoid receptor antagonists (MRAs). The next-generation non-steroidal MRAs are under investigations. New medications including calcium channel blockers, macrophage antibiotics, and aldosterone synthase inhibitors have provided a new perspective for the medical treatment of PA.

Antagonistas do Sistema Renina-Angiotensina e Betabloqueadores na Prevenção da Cardiotoxicidade por Antraciclinas: Revisão Sistemática e Metanálise / Renin-angiotensin System Antagonists and Beta-blockers in Prevention of Anthracycline Cardiotoxicity: a Systematic Review and Meta-analysis

Resumo Fundamento As evidências que embasam o uso de inibidores do sistema-renina-angiotensina aldosterona (SRAA) e betabloqueadores para prevenção de cardiomiopatia induzida por antraciclinas são controversas. Objetivo Realizamos uma metanálise para avaliar a eficácia desses medicamentos na prevenção da cardiotoxicidade. Métodos A metanálise incluiu estudos prospectivos e randomizados com adultos submetidos à quimioterapia com antraciclina e comparou o uso de terapias SRAA ou betabloqueadores versus placebo com seguimento de 6 a 18 meses. O desfecho primário foi alteração da fração de ejeção do ventrículo esquerdo (FEVE) durante a quimioterapia. Os desfechos secundários foram: a incidência de insuficiência cardíaca, mortalidade por todas as causas e alterações na medida do diâmetro diastólico final. A avaliação da heterogeneidade foi realizada por estratificação e meta-regressão. O nível de significância adotado foi p < 0,05. Resultados A busca resultou em 17 estudos, totalizando 1.530 pacientes. A variação (delta) da FEVE foi avaliada em 14 estudos. A terapia neuro-hormonal foi associada a um menor delta na FEVE pré-terapia versus pós-terapia (diferença média ponderada 4,42 [intervalo de confiança de 95% 2,3 a 6,6]) e maior FEVE final (p < 0,001). O tratamento resultou em menor incidência de insuficiência cardíaca (risk ratio 0,45 [intervalo de confiança de 95% 0,3 a 0,7]). Não houve efeito na mortalidade (p = 0,3). Para a análise da FEVE, foi documentada heterogeneidade substancial, não explicada pelas variáveis exploradas no estudo. Conclusão O uso de inibidores do SRAA e betabloqueadores para prevenção da cardiotoxicidade induzida por antraciclinas foi associado a redução menos pronunciada da FEVE, maior FEVE final e menor incidência de insuficiência cardíaca. Não foram observadas alterações na mortalidade. (CRD PROSPERO 42019133615)

Abstract Background The evidence supporting the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and beta-blockers for the prevention of anthracycline-induced cardiomyopathy is controversial. Objective We performed a meta-analysis to assess the effectiveness of these drugs in preventing cardiotoxicity. Methods The meta-analysis included prospective, randomized studies in adults receiving anthracycline chemotherapy and compared the use of RAAS inhibitors or beta-blockers versus placebo with a follow-up of 6 to 18 months. The primary outcome was change in left ventricular ejection fraction (LVEF) during chemotherapy. Secondary outcomes were the incidence of heart failure, all-cause mortality, and changes in end-diastolic measurement. Heterogeneity was assessed by stratification and meta-regression. A significance level of p < 0.05 was adopted. Results The search resulted in 17 studies, totaling 1,530 patients. The variation (delta) in LVEF was evaluated in 14 studies. Neurohormonal therapy was associated with a lower delta in pre- versus post-therapy LVEF (weighted mean difference 4.42 [95% confidence interval 2.3 to 6.6]) and higher final LVEF (p < 0.001). Treatment resulted in a lower incidence of heart failure (risk ratio 0.45 [95% confidence interval 0.3 to 0.7]). There was no effect on mortality (p = 0.3). For analysis of LVEF, substantial heterogeneity was documented, which was not explained by the variables explored in the study. Conclusion The use of RAAS inhibitors and beta-blockers to prevent anthracycline-induced cardiotoxicity was associated with less pronounced reduction in LVEF, higher final LVEF, and lower incidence of heart failure. No changes in mortality were observed. (CRD PROSPERO 42019133615)

Nueva evidencia en el tratamiento de la enfermedad renal diabética: ¿qué aporta la finerenona?

Contexto: la enfermedad renal diabética (ERD) es la primera causa a nivel mundial de enfermedad renal crónica (ERC) e impacta directamente en el riesgo cardiovascular y mortalidad de los pacientes con diabetes mellitus (DM). La finerenona, un antagonista selectivo del receptor mineralocorticoide (ARM), ha sido descrito en diversos estudios recientes como un fármaco que contribuye a la reducción de la progresión de la ERD y la disminución del riesgo cardiovascular, con un adecuado perfil de seguridad. Objetivo: realizar una revisión de la literatura sobre el impacto de la finerenona en la progresión del daño renal y el riesgo cardiovascular en los pacientes con ERD. Metodología: se realizó una búsqueda sistemática en diversas fuentes: PubMed (Medline, Biblioteca del Congreso de los Estados Unidos), Science Direct, Scopus, Embase y Lilacs; la búsqueda fue restringida a referencias en idioma español e inglés, sin límites en la fecha de publicación. Se utilizaron las siguientes palabras clave en el idioma inglés: diabetic renal disease, chronic kidney disease, diabetes mellitus, spironolactone, eplerenone, finerenone, mineralocorticoid receptor antagonist y sus correspondientes versiones en español. Resultados: Las referencias encontradas en la búsqueda fueron revisadas entre los diferentes autores para, posteriormente, proceder a realizar la elaboración del documento. Conclusiones: la finerenona es un medicamento que brinda cardio y nefroprotección en pacientes con ERD de fenotipo albuminúrico.

Background: Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) worldwide and has a direct impact on cardiovascular risk and mortality in patients with diabetes mellitus (DM). Finerenone, a selective mineralocorticoid receptor (MRA) antagonist, has been described in several recent studies as a drug that contributes to slowing the progression of CKD and reducing cardiovascular risk, with an adequate safety profile. Purpose: To carry out a review of the literature on the impact of finerenone on the progression of renal damage and cardiovascular risk in patients with DKD. Methodology: A systematic search were carried out in various sources: PubMed (Medline, United States Library of Congress), Science Direct, Scopus, Embase and Lilacs; the search was restricted to references in Spanish and English, with no limits on publication date. The following keywords in the English language were used: diabetic renal disease, chronic kidney disease, diabetes mellitus, spironolactone, eplerenone, finerenone, mineralocorticoid receptor antagonist and their corresponding Spanish versions. Results: The references found in the search were reviewed among the different authors to subsequently proceed to prepare the document. Conclusions: Finerenone is a drug that provides cardio and nephroprotection in patients with DKD albuminuric phenotype.

Effect of wheat-grain moxibustion on the expression of 5-HT and cortisol in the serum, and MR and GR in the hippocampus in rats with hypothyroidism complicated with depression / 中国针灸

OBJECTIVE@#To observe the effect of wheat-grain moxibustion on behavior, 5-hydroxytryptamine (5-HT) and cortisol in the serum, mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus in rats with hypothyroidism complicated with depression, and to explore the possible mechanism of wheat-grain moxibustion on improving depression in rats with hypothyroidism.@*METHODS@#A total of 32 SPF SD rats were randomly divided into a blank group, a model group, a medication group and a wheat-grain moxibustion group, 8 rats in each group. Except for the blank group, the rats in the remaining groups were treated with intragastric administration of 0.1% propylthiouracil (PTU) suspension at 1 mL/100 g, once a day for 4 weeks to establish the rat model of hypothyroidism, and whether the rats were accompanied with depression-like behavior determined through behavioristics evaluation. The rats in the medication group were intervened with euthyrox at 0.9 mL/100 g, once a day, for 4 weeks; the rats in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14), "Mingmen" (GV 4), "Shenshu" (BL 23) and "Pishu" (BL 20), 7 cones each acupoint, once a day, six times a week for 4 weeks. After the intervention, the depression status was observed by behavioristics test; the contents of thyroid stimulating hormone (TSH), total thyroxine (TT4), 5-HT and cortisol in the serum were detected by ELISA; the protein expressions of MR and GR in hippocampus were detected by Western blot; the expressions of MR mRNA and GR mRNA in the hippocampus were detected by real-time PCR.@*RESULTS@#Before the intervention, compared with the blank group, the scores of open field test (OFT) were decreased and the immobility time of tail suspension test (TST) was prolonged (P<0.05); the serum TSH contents were increased and TT4 contents were decreased (P<0.01) in the other three groups. After the intervention, compared with the model group, the vertical score of OFT was increased and the immobility time of forced swimming test (FST) was prolonged in the medication group (P<0.05), while the scores of three items of OFT were increased (P<0.05, P<0.01), and the immobility time of FST and TST was shortened in the wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the medication group, the immobility time of TST and FST in the wheat-grain moxibustion group was shorter (P<0.05, P<0.01). Compared with the blank group, in the model group, the contents of serum TSH and cortisol were increased (P<0.01, P<0.001), while the contents of serum TT4 and 5-HT were decreased (P<0.01, P<0.001). Compared with the model group, the contents of serum TT4 and 5-HT were increased, while the contents of serum TSH and cortisol were decreased in the medication group and wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the blank group, the protein and mRNA expression of MR, GR in the hippocampus in the model group was decreased (P<0.01, P<0.05, P<0.001); compared with the model group, the protein and mRNA expression of MR in the hippocampus in the medication group were increased (P<0.05), and the protein expression of MR, GR and mRNA expression of MR in the hippocampus in the wheat-grain moxibustion group were increased (P<0.05, P<0.01). Compared with the medication group, the expression of MR mRNA in the wheat-grain moxibustion group was increased (P<0.05).@*CONCLUSION@#Wheat-grain moxibustion could significantly improve thyroid function and depression in rats with hypothyroidism. Its mechanism may be related to up-regulating the protein and mRNA expression of MR and GR in the hippocampus, and then affecting the expression of serum cortisol and 5-HT.

Effect of Sinisan on BDNF/TrkB， 5-HT/5-HT1AR， and HPA axis in Depression Model Rats / 中国实验方剂学杂志

Objective:To observe the effect of Sinisan on the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TrKB）， 5-hydroxytryptamine （5-HT）/5-HT1A receptor （5-HT1AR）， and hypothalamus-pituitary-adrenal （HPA） axis in depressed rats， and explore the antidepressant mechanism of Sinisan based on BDNF/TrKB， 5-HT/5-HT1AR， and HPA axis. Method:A total of 120 male Wistar rats were randomly divided into a normal group， a model group， a fluoxetine （0.01 g·kg^-1） group， and low- （1.25 g·kg^-1）， medium- （2.5 g·kg^-1）， and high-dose （5 g·kg^-1） Sinisan groups， with 20 rats in each group. The depression model was induced by isolation combined with chronic unpredictable mild stimulation（CUMS） in rats except for those in the normal group for 21 days. Rats were then treated correspondingly once a day for 21 days by gavage. Those in the normal group and the model group received an equal volume of normal saline. During the intervention， the model rats were stimulated continuously. The depressive state of CUMS model rats was evaluated by sucrose preference test and open field test. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of corticotropin-releasing hormone （CRH）， adrenocorticotropic hormone （ACTH）， and corticosterone （CORT） in the plasma and BDNF and 5-HT levels in the hippocampal homogenate. The mRNA expression of hippocampal TrKB， 5-HT1AR， glucocorticoid receptor （GR）， and mineralocorticoid receptor （MR） was detected by real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR）. The protein expression of hippocampal TrKB， 5-HT1AR， GR， and MR was detected by Western blot. The histomorphological changes of the hippocampus were observed by hematoxylin-eosin （HE） staining. Result:Compared with the normal group， the model group showed decreased sucrose preference rate （<italic>P</italic><0.01）， reduced horizontal and vertical scores in the open field test （<italic>P</italic><0.01）， increased plasma content of CRH， ACTH， and CORT （<italic>P</italic><0.01）， declining content of BDNF and 5-HT in the hippocampus （<italic>P</italic><0.01）， dwindled mRNA and protein expression levels of TrKB， 5-HT1AR， and GR （<italic>P</italic><0.01）， elevated mRNA and protein expression of MR （<italic>P</italic><0.01）， and damaged hippocampal neurons revealed by HE staining. Compared with the model group， the groups with drug intervention showed increased sucrose preference rate （<italic>P</italic><0.01） and horizontal and vertical scores in the open field test （<italic>P</italic><0.05， <italic>P</italic><0.01）， decreased content of plasma CRH， ACTH， and CORT （<italic>P</italic><0.05， <italic>P</italic><0.01）， elevated content of hippocampal BDNF and 5-HT （<italic>P</italic><0.05， <italic>P</italic><0.01）， elevated mRNA and protein expression levels of hippocampal TrKB， 5-HT1AR， and GR （<italic>P</italic><0.05， <italic>P</italic><0.01）， reduced mRNA and protein expression levels of hippocampal MR （<italic>P</italic><0.05， <italic>P</italic><0.01）， and recovered hippocampal neurons as revealed by HE staining. Conclusion:Sinisan can exert a significant antidepressant effect by increasing hippocampal BDNF and 5-HT content， up-regulating TrKB， 5-HT1AR， and GR mRNA and protein expression， down-regulating MR mRNA and protein expression， inhibiting HPA axis hypertrophy， and enhancing the regeneration and repair of hippocampal neurons.

Management of Infants with Congenital Adrenal Hyperplasia

Treatment of congenital adrenal hyperplasia (CAH) requires lifelong replacement of glucocorticoids with regular follow up to manageassociated morbidities. The current review focuses on follow-up and management of infants diagnosed with classical CAH pertinent toIndian context. Early initiation of oral hydrocortisone in divided doses is recommended after diagnosis in newborn period, infancy andchildhood. Fludrocortisone is recommended for all infants with classical CAH. All infants should be monitored as per protocol fordisease and treatment related complications. The role of prenatal steroids to pregnant women with previous history of CAH affectedinfant for prevention of virilization of female fetus is controversial.

Research progress of the effect of cell-specific mineralocorticoid receptor on blood pressure regulation / 解放军医学杂志

The extrarenal effects of mineralocorticoid receptor (MR) activation are closely related to the regulation of blood pressure. The activation ability of MR varied with age and gender in blood pressure regulation. MR of different types of cells play an important role in the pathogenesis of hypertension by increasing the expressions of osteogenic transcription factors, epithelial sodium channels, fibrotic substances and fibrogenic factors, change of vascular L-type calcium channels, aggravation of inflammation and oxidative stress, etc., leading to arterial elasticity weakened, myocardial fibrosis, and water sodium retention. Cell-specific MR block provides a theoretical basis for the development of targeted drugs for treatment of hypertension in the future. The effect of cell-specific MR on the regulation of blood pressure has been reviewed in present paper.

Antagonistas de mineralocorticoides en coriorretinopatía central serosa crónica / Mineralocorticoid receptor antagonists in chronic central serous chorioretinopathy

INTRODUCCIÓN: La coriorretinopatía central serosa consiste en la filtración de fluido desde la coroides y su acumulación en el espacio subretinal. Su forma crónica se asocia a pérdida visual permanente. Los antagonistas de mineralocorticoides son una alternativa de tratamiento para esta patología, aunque no existe evidencia clara sobre su efectividad. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos tres revisiones sistemáticas que en conjunto incluyeron 22 estudios primarios, de los cuales, cuatro corresponden a ensayos aleatorizados. Concluimos que el uso de antagonistas de mineralocorticoides en coriorretinopatía central serosa crónica probablemente resulta en poca o nula diferencia en la agudeza visual corregida. No es posible establecer con claridad si su uso disminuye el grosor del fluido subretinal, debido a que la certeza de la evidencia ha sido evaluada como muy baja. Además, esta intervención podría resultar en poca o nula diferencia en la aparición de efectos adversos, pero la certeza de la evidencia es baja.

INTRODUCTION: Central serous chorioretinopathy consists of the leakage of fluid from the choroid and its accumulation into the subretinal space. Its chronic form is associated with permanent vision loss. Mineralocorticoid receptor antagonists are an alternative treatment for this condition, although there is no clear evidence about their effectiveness. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified three systematic reviews including 22 studies overall and four of them are randomized trials. We concluded that in chronic central serous chorioretinopathy, mineralocorticoid receptor antagonists probably make little or no difference to best-corrected visual acuity. We are uncertain whether this intervention reduces subretinal fluid height because the certainty of the evidence is very low. Furthermore, this intervention may make little or no difference in terms of adverse effects, but the certainty of the evidence is low.

Diabetes mellitus e insuficiencia cardíaca: nuevas perspectivas en el tratamiento farmacológico / Diabetes and heart failure: new perspectives in pharmacological treatment

La Diabetes Mellitus (DM) y la Insuficiencia Cardíaca (IC) son enfermedades crónicas cuyas prevalencias han ido en aumento y que determinan una mayor mortalidad de los pacientes que las padecen. La relación de ambas enfermedades es conocida como "Miocardiopatía Diabética" (MD). Los eventos fisiopatológicos principales de la MD son el mal control glicémico, el aumento de captación de ácidos grasos por parte de las células cardiacas, la disfunción endotelial y la remodelación cardíaca. Los nuevos tratamientos, se han enfocado en tratar tanto el control glicémico como la remodelación cardíaca. Los principales exponentes de los fármacos antidiabéticos favorables para la IC en pacientes con DM son los inhibidores del cotransportador de Sodio-Glucosa renal SGLT2 (iSGLT2), y los agonistas del receptor de GLP-1 (aGLP-1). Otros fármacos de relevancia son los antagonistas del receptor de mineralocorticoides (aRMC). Se realiza una revisión de la fisiopatología y del manejo actualizado de la IC en pacientes con DM.

Diabetes Mellitus (DM) and Heart Failure (HF) are chronic diseases whose prevalences have risen and which increase patient mortality. The two diseases are inter-related in what is called "Diabetic Cardiomyopathy" (DC). The main pathophysiological characteristics of cardiomyopathy are poor glycemic control, a rise in the capture of fatty acids by cardiac cells, endothelial dysfunction and cardiac remodeling. The principal anti-diabetic medications beneficial for HF in DM patients are renal sodium-glucose cotransporter-2 inhibitors (SGLT2) and GLP-1 receptor agonists (GLP-1RAs). Other relevant medications are mineralocorticoid receptor antagonists (MRA). We review the pathophysiology and current management of HF in diabetic patients.

Inhibition of mineralocorticoid receptor activation by eplerenone to reduce autophagy in obstructive nephropathy / 中国药理学通报

Aim To observe the effect of mineralocorticoid receptor blocker eplerenone on autophagy in obstructive nephropathy and its mechanism. Methods Totally 36 male Wistar rats were randomly divided into sham-operation group, model group and eplerenone group. The animal models were established with unilarteral urteral obstruction ( UUO). The rats in eplerenone group were treated with eplerenone (100 mg • kg"1 • d"1). The obstructed kidneys were collected lOd after UUO. The expression of NR3C2 was detected by laser confocal microscopy, the expression of serum and glucocorticoid-induced protein kinase 1 ( SGK-1), phosphorylated mammal target of rapamycin (p-mTOR) , autophagy associated gene 5 (Atg5) , Be-clin-1 and microtubular-associated protein 1 light chain 3 (LC3) were detected by immunohistochemistry and Western blot. Results The expression of NR3C2 was detected in cytoplasm of renal tubular distal epithelial cells, but not in nucleus in sham-operation group with laser confocal microscopy. The expression of NR3C2 was enhanced significantly in model group, mainly in nucleus but significantly inhibited in eplerenone group. The immunohistochemistry and Western blot showed that the expressions of SGK-1, Atg5, Beclin-1 and the ratio of LC3 11/I in model group were up-regulated and down-regulated by eplerenone treated group. The expression of p-mTOR was down-regulated in model group compared with sham-operation group and up-regulated in eplerenone group. Conclusions Eplerenone plays a role in reducing autophagy in obstructive nephropathy via inhibiting the activation of mineralocorti-coid receptor.

An update on evidence for mineralocorticoid receptor antagonist in the treatment of central serous retinopathy / 中华眼底病杂志

As most patients of central serous retinopathy (CSC),the symptoms of acute onset will alleviate by oneself after 4-6 months.About 30％-50％ of patients with CSC experience chronic or recurrent cases.Resulting in persistent neurosensory detachments and subretinal fluid,causing significant vision loss.Mineralocorticoid receptor (MR) is a kind of nuclear hormone receptors,plays a role in theregulation of water and electrolyte balance.Excessive MR signaling is associated with many diseases.Study found that MR antagonists decreased the thickness of the retina and improved in vision,there was no serious adverse reactions during the period of treatment.Initial dose of MR antagonists was 25 mg per day,1 week later,dosage was increased to 50 mg per day,and treatment for about 3 months.There is no conclusive effective treatment and the dosage are still unknown.MR antagonists may be a safe and effective way to treat CSC,though evidence is scant.Prospective,multicenter,large-scale trials is required.

Research progress of apparent mineralocorticoid excess syndrome / 中国基层医药

Apparent mineralocorticoid excess (AME) is an autosomal recessive inheritance caused by 11β－hydroxysteroid dehydrogenase 2 gene mutation.It may occur in newborn and adult.AME was first reported in 1977 by Werder et al.Its clinical features include hyporenin type hypertension , hypoaldosteronemia, metabolic alkalosis, hypernatremia and hypokalemia.In recent years,with the improvement of clinical diagnosis ,especially gene detection , AME has been reported one after another.In this paper,the pathogenesis,clinical manifestation ,diagnosis and therapy of AME were reviewed in order to improve the understanding of this disease and provide reference for its clinical diagnosis and treatment.

Estudio e identificación de microRNA en exosomas urinarios en hipertensión arterial mineralocorticoide / Study and identification of microRNA in urinary exosomes in mineralocorticoid arterial hypertension

About 15% of the essential hypertensive patients would have a low activity of the 11ßHSD2 enzyme, which inactivates cortisol (F) to cortisone (E). Gene expression can be negatively regulated by miRNA. Urinary exosomes and their specific content (miRNA/proteins) represent a valuable tool as a biomarker for the diagnosis and prognosis of the disease. Aim: To evaluate the expression of miRNA specific for 11ßHSD2 in samples of urinary exosomes and to determine its association with biochemical variables associated with mineralocorticoid metabolism. Subjects and Methods: Cross-sectional study in subjects between 10-60 years. They were classified into subjects with high F/E (> p75) and low cortisone (< p25) and control subjects. The urinary exosomes were isolated with the Invitrogen kit. Bioinformatic analysis was performed with Mir Walk to identify specific miRNAs of HSD11B2. The expression of miRNA was evaluated by qRT PCR. The comparisons were made with the Mann-Whitney test. Results: 7.1% of the subjects are suggestive of a partial deficiency of 11ßHSD2 (NC-AME). The expression of miR-488 was higher in NC-AME than in controls (5839 ± 1719 vs 3,437 ± 2,581; p = 0.01). We found positive associations between mir-615 and ARP; miR-488 and the sodium/potassium ratio; miR-1205 with age and urinary sodium excretion; miR-494 with age, activity MMP9 and NGAL. Conclusion: We identified high expression of miR488 in NC-AME subjects and associations of miRNAs with biochemical variables associated with mineralocorticoid metabolism. Thus, exosomes and their miRNA content could be potential regulators and biomarkers of 11ßHSD2 activity.

Efficacy of low-dose spironolactone on top of angiotensin receptor blockade in patients with glomerulonephritis

BACKGROUND: Previous studies have shown that aldosterone antagonists have a proteinuria-lowering effect in patients with proteinuria and progressive proteinuric disease not adequately controlled by the use of angiotensin receptor blockers (ARBs). Aldosterone antagonists, in combination with ARBs, might improve proteinuria in patients with glomerulonephritis (GN). METHODS: In the present retrospective study, we evaluated the proteinuria-lowering effect and drug safety of low-dose spironolactone (12.5 mg/day) in 42 patients with GN being treated with an ARB. RESULTS: Proteinuria decreased from a mean total-protein-to-creatinine (TP/Cr) ratio of 592.3 ± 42.0 mg/g at baseline to 335.6 ± 43.3 mg/g after three months of treatment with spironolactone (P < 0.001). After the initial three months, the mean TP/Cr ratio increased progressively at six, nine, and 12 months; however, it was still less than the baseline value (P = 0.001, < 0.001, and < 0.001, respectively). Although serum Cr levels increased significantly at three and nine months compared with baseline (P = 0.036 and 0.026, respectively), there was no time effect of treatment (P = 0.071). Serum potassium levels tended to increase with time (P = 0.118), whereas systolic and diastolic blood pressures decreased with time (P = 0.122 and 0.044, respectively). CONCLUSION: Low-dose spironolactone in combination with an ARB reduced proteinuria in patients with GN, which could represent a novel treatment option in individuals whose proteinuria is not optimally controlled by the use of ARBs alone.

Mechanism of Shenluotong regulating NR3C2/SGK-1/Smad pathway in inhibiting renal interstitial fibrosis / 中草药

Objective To investigate the mechanism of Shenluotong inhibiting renal interstitial fibrosis by regulating NR3C2/SGK-1/Smad pathway. Methods A total of 48 Wistar rats were randomly divided into sham operation group, model group, Eplerenone group, and Shenluotong group (n = 12). Model group, Eplerenone group, and Shenluotong group used unilateral ureteral obstruction (UUO) method to establish rat renal interstitial fibrosis model. After the operation, the rats in the eplerenone group were treated with eplerenone at a dose of 100 mg/(kg∙d). Rats in the Shenluotong group were oral given Shenluotong decoction at a dose of 26 g/(kg∙d) and Sham operation group and model group were administrated equal volume of saline once daily for continuous 10 d. Laser confocal microscopy was used to detect mineralocorticoid receptor NR3C2 expression. The expressions of SGK-1, TGF-β1, Smad4, and Smad7 in renal tissues were detected by immunohistochemistry, Western Blot and Real time-PCR. Results In the sham operation group, NR3C2 was expressed in the cytoplasm of renal tubular epithelial cells and was not expressed in the nucleus. The expression of NR3C2 in the UUO rat was significantly up-regulated in cytoplasm and positive expression was observed in the nucleus. The expression of NR3C2 in the nucleus of cells in the Eplerenone group and Shenluotong group was significantly decreased when compared with the model group. Compared with the sham-operated group, the expression of SGK-1, TGF-β1, and Smad4 was significantly up-regulated and the expression of Smad7 was significantly decreased (P < 0.05, 0.01) in the other groups. Compared with model group, the expression range and intensity of TGF-β1 and Smad4 were significantly decreased in Eplerenone group and Shenluotong group (P < 0.05, 0.01), and the expression range and intensity of Smad7 were significantly increased (P < 0.01). Conclusion Shenluotong can inhibit renal interstitial fibrosis through blocking the activation of mineralocorticoid receptor, reducing the level of SGK-1, and regulating the Smads signal pathway to inhibit the overexpression of TGF-β1.

Mineralocorticoid receptor in ocular fundus diseases / 中华眼底病杂志

The mineralocorticoid receptor (MR) belongs to the nuclear receptor superfamily and is expressed in the retina and choroid. MR antagonist (MRA) has a long history of application in non-ophthalmic clinical practice. Various cellular and animal models indicated that inappropriate activation of MR participated in pathological angiogenesis, oxidative stress, inflammation, disturbance of ion/water homeostasis and neurodegenerative changes, while the application of MRA can reduce or reverse these pathological processes. After using MRA in central serous chorioretinopathy (CSC) patients, improved visual function, less subretinal fluid and reduced sub-foveal choroidal thickness were observed. Single nucleotide polymorphisms in MR and plasma aldosterone levels were significantly different between chronic CSC patients and CSC patients with spontaneous remission. Novel formulation for sustained-release MRA and the mechanisms involving inflammation may become the new focus of MR study. This review summarizes the research status of MR and MRA in order to provide a reference for future basic research and clinical treatment.

The status of the oral drugs for chronic central serous chorioretinopathy / 中华眼底病杂志

Chronic central serous chorioretinopathy (CSC) usually demonstrates frequent recurrence,diffuse leakage and persistent subretinal fluid,which cannot be absorbed,thus lead to photoreceptor damage and poor visual acuity.As glucocorticoids have been implicated in the pathogenesis of chronic CSC,various anti-glucocorticoids oral drugs were used in the clinic to promote retinal fluid absorption and reduce the central retinal thickness of the macula and improve the vision outcomes.In addition,the 5α-reductase-specific inhibitor finasteride,the P450-3A4 inducer rifampicin,circadian rhythmic regulator melatonin,and systemic anti-inflammatory drug methotrexate have also been put into clinical trials for chronic CSC,and achieved certain effects.However,most of the clinical studies on these oral drugs were case reports,but not multi-center randomized clinical trials.The long-term effects of these oral drugs need to be observed and studied further.

Pseudohipoaldosteronismo y aparente exceso de mineralocorticoides: cara y ceca en dos pacientes pediátricos / Pseudohypoaldosteronism and apparent mineralocorticoid excess: two faces, two pediatric patients

Los síndromes endocrinológicos con hipofunción o hiperfunción con niveles paradójicos de dosajes hormonales han sido bien caracterizados en los últimos años del siglo XX, a partir del desarrollo de técnicas genéticas y moleculares. Presentamos dos pacientes con pseudohipoaldosteronismo y aparente exceso de mineralocorticoides como síndromes en espejo, con la intención de alertar al médico clínico respecto de su consideración como entidad diagnóstica en niños con alteraciones hidroelectrolíticas. (AU)

Endocrinological syndromes with underactive or overactive hormonal levels with paradoxical dosages have been well characterized over the years of the twentieth century, from the development of genetic and molecular techniques. We present two patients with pseudohypoaldosteronism and apparent mineralocorticoid excess as mirror syndromes, with the aim to alert the clinician regarding their consideration as a diagnostic entity in children with fluid and electrolyte disturbances. (AU)

Aldosterona e IL-17 en la génesis de la hipertensión arterial mineralocorticoídea, un estudio ex vivo / Aldosterone and il-17 in the genesis of mineralocorticoid arterial hypertension: an ex vivo study

Background: Treatment of dendritic cells (DC) with aldosterone induces the secretion of IL-6 and TGF-beta. The polarization of naïve T cells to helper 17 T lymphocytes with DCs pre-incubated with aldosterone, has been described in vivo, generating an IL-17 hyper-secreting phenotype, a cytokine associated with cardiac and renal fibrosis. There are mineralocorticoid receptors (MR) in immune cells and their activation may determine the inflammatory (M1) or adaptive (M2) macrophage phenotype. Aldosterone levels could regulate immunogenic gene expression in these cells, modulating the liberation of specific cytokines. Aim: To assess in humans the association of aldosterone levels and IL-17 with inflammatory markers in peripheral blood mononuclear cells (PBMC). Material and Methods: In blood samples of 176 participants aged 18 to 67 years (61 percent women) with a body mass index of 27.1 +/- 4.8 kg/m2, aldosterone, plasma renin activity (ARP), cortisol, C reactive protein, andIL-17 were measured. mRNA was isolated from PBMCs to measure the expression of MR RAC-1, HO-1, TLR-4, CD-14, NGAL and IL-17 by real time polymerase chain reaction. Results: Aldosterone correlated positively with ARP and the expression of CD-14 in PBMCs. Plasma levels of IL-17 were positively associated with the expression of MR, Rac1a and NGAL. Conclusions: Aldosterone and IL-17 levels were associated with inflammatory activation markers in PBMC, which could activate MRand promote a subclinical inflammatory status inducing hypertension.

Effect of lipopolysaccharide-mediated infection during pregnancy on the expression of mineralocorticoid receptor and dendritic spines in hippocampus of rat offspring / 中华实用儿科临床杂志

Objective To observe the effect of lipopolysaccharide (LPS)-mediated infection during pregnancy on the expression of mineralocorticoid receptor (MR) and density of dendritic spines in CA1 region of the dorsal hippocampus of rat offspring,so as to explore the mechanisms for learning and memory injury of rat offspring which were infected during prenatal period,then to provide scientific experimental evidence for the prevention of prenatal infection-induced delayed neuropsychiatric sequelae which contributed to learning and memory dysfunction.Methods Ten-week-old female Sprague-Dawley rats (n =30) were matched with male rats (1 ∶ 1).Pregnant rats were randomly divided into a control group (n =10) and an experimental group (n =20).The pregnant rats in experimental group were treated with LPS (66 μg/kg,intraperitoneally),and the pregnant rats in control group were intraperitoneally injected with same volume of saline on gestational day 10.On postnatal day 48,Morris water maze was used to estimate the ability of learning and memory;the brain tissues of offspring were taken and paraffin sections were stained with hematoxylin eosin (HE) for histological observation of CA1 region of the dorsal hippocampus;frozen sections were treated with indirect immunofluorescence to observe the expression of MR in CA1 region of the dorsal hippocampus;Golgi-Cox method was used to observe the density of dendritic spines of CA1 region.Results In Morris water maze test,from the third day the time of escape latency in experimental group [the 3rd day:(42.603 ± 9.837) s;the 4th day:(30.222 ± 9.789) s;the 5th day:(28.808 ± 12.526) s] was significantly higher than that of the control group [the 3rd day:(28.078±14.088) s;the 4th day:(20.692±13.099) s;the 5th day:(14.632 ±11.624) s] (the 3rd day:t =-3.274,P＜0.01;the 4th day:t =-2.257,P ＜0.05;the 5th day:t =-3.213,P＜0.01);the swimming time in the target quadrant [(14.660 ± 7.337) times] and the number of crossing platform [(0.933 ± 0.704) times] in experi mental group were significantly decreased compared with those of the control group [time:(23.820 ± 6.321) s;num bers:(2.000 ± 0.756) times] (t =3.663,4.000,all P ＜ 0.01).Hematoxylin eosin staining showed that the nerve cells of the hippocampus in the control group distributed in order,nucleuses were round or oval,nucleoli were obvious,and chromatins were homogeneous;but the cells in the experimental group distributed in disorder and pathological changes were detected,such as cellular swelling,necrosis and obvious nuclear pyknosis.By immunofluorescence staining,the average optical density (AOD) of MR in CA1 region decreased significantly in the experimental group (0.067 ± 0.017) compared with that of the control group (0.083 ± 0.009) (t =2.644,P ＜ 0.05).In Golgi-Cox method,the density of dendritic spines in experimental group [(7.705 ± 0.791)/10 μm] was below that of the control group [(9.655 ± 1.391)/10 μm] (t =3.852,P ＜ 0.01).Conclusions LPS-mediated infection during pregnancy might lead to hippocampus-dependent learning and memory dysfunction which might be associated with the reduced expression of MR and the low density of dendritic spines in CA1 region of the dorsal hippocampus.