Association of asymmetric dimethylarginine with the pathological process of persistent pulmonary hypertension of the newborn / 中国当代儿科杂志

OBJECTIVES@#To study the change in asymmetric dimethylarginine (ADMA) in the circulation system of full-term infants with persistent pulmonary hypertension of the newborn (PPHN) and its association with treatment response, as well as the possibility of ADMA as a therapeutic target and a marker for treatment response.@*METHODS@#A prospective study was performed. A total of 30 full-term neonates who were diagnosed with PPHN within 3 days after birth were enrolled as the PPHN group, and the neonates without PPHN, matched for gestational age and age, who were treated or observed in the department of neonatology were enrolled as the control group. Serum samples were collected on days 1, 7, and 14 of treatment. The high-performance liquid chromatography-tandem mass spectrometry was used to measure the serum concentrations of L-arginine, ADMA, and its isomer symmetric dimethylarginine (SDMA).@*RESULTS@#For the neonates in the control group, the serum concentrations of ADMA and L-arginine continuously increased and the serum concentration of SDMA continuously decreased within the first 14 days of treatment. On days 1 and 14, there was no significant difference in the serum concentration of ADMA between the control and PPHN groups (P>0.05). On day 7, the PPHN group had a significantly higher serum concentration of ADMA than the control group (P<0.05), while there were no significant differences in serum concentrations of SDMA or L-arginine (P>0.05). Moreover, after 7 days of treatment, the PPHN neonates with a systolic pulmonary arterial pressure (sPAP) of >35 mmHg had a significantly higher serum concentration of ADMA than those with an sPAP of ≤35 mm Hg.@*CONCLUSIONS@#There are continuous increases in the ADMA concentration and the ADMA/SDMA ratio in the circulation system of full-term infants within the first 2 weeks after birth, and this process is accelerated by the pathological process of PPHN, suggesting that ADMA may be involved in the pathologic process of PPHN. A high level of ADMA is associated with the resistance to PPHN treatment, suggesting that inhibition of ADMA might be a potential target of drug intervention to improve the treatment response of PPHN.

Do the Different Types of Pulmonary Hypertension Cause the Same Effect on Right Heart and Serum Asymmetrical Dimethylarginine Levels in Female Patients?

ABSTRACT Objective: Right-heart function is a major determinant of clinical outcome in patients with elevated pulmonary artery pressure due to pulmonary venous hypertension (PVH) and pulmonary arterial hypertension (PAH). Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. This study aimed to evaluate if different types of pulmonary hypertension (PH) would cause the same effect on right-heart functions and serum ADMA levels in female patients. Methods: This study included patients with PAH as group I, patients with PVH due to mitral stenosis (mitral valve area ≤ 1.5 cm2, without any additional valve or left-heart disease and systolic pulmonary artery pressure ≥ 50 mmHg in transthoracic echocardiography) as group II, and healthy control subjects as group III. Transthorasic echocardiographic evaluations for right-heart functions were performed according to the guidelines of the American Society of Echocardiography. Venous blood samples were collected, and the serum ADMA concentrations were obtained with the ELISA kit (DRG® International Inc., Springfield, NJ, USA). Results: Patients in groups I and II had higher ADMA levels than healthy control subjects. Right-atrium area and dimensions, right-ventricular (RV) volumes, grade of tricuspid regurgitation, systolic pulmonary arterial pressure, RV wall thickness, and RV outflow tract diameters were significantly higher in group I patients than in group II patients. Right-ventricular myocardial performance index was lower, and RV fractional area change and tricuspid valve systolic tissue Doppler velocity were higher in group II patients than in group I patients. Conclusion: This study demonstrated that both PAH and PVH caused increase in right-heart dimensions and impairment in right-heart functions.

Effect of acupuncture on vascular endothelial function in patients of polycystic ovary syndrome with different glucose tolerance status / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture on vascular endothelial function in patients of polycystic ovary syndrome (PCOS) with impaired glucose tolerance (IGT) and normal glucose tolerance (NGT).@*METHODS@#A total of 140 patients with PCOS were divided into an IGT group (70 cases, 11 dropped off) and a NGT group (70 cases, 9 cases dropped off). The patients in the two groups were treated with full-cycle acupuncture at Zhongwan (CV 12), Guanyuan (CV 4), Qihai (CV 6), Tianshu (ST 25), etc. once every other day, 3 times a week, for 3 months. Before and after treatment, TCM symptom score, insulin resistance index [including fasting plasma glucose (FPG), 2-hour blood glucose (2hPG), fasting serum insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR)] and vascular endothelial related factors [including asymmetric dimethylarginine (ADMD), endothelin-1 (ET-1), malondialdehyde (MDA), nitric oxide (NO)] were compared between the two groups; in addition, the obese subgroup and non-obese subgroup of the two groups were further compared.@*RESULTS@#Compared before treatment, the TCM symptom scores, ADMD, ET-1 and MDA after treatment were decreased (@*CONCLUSION@#Acupuncture could improve vascular endothelial function in PCOS patients, IGT patients have better efficacy than NGT patients, and obese patients have better efficacy than non-obese patients.

Effect of asymmetric dimethylarginine on development of atherosclerosis in patients with chronic kidney disease / 上海交通大学学报（医学版）

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor and is associated with the incidence of atherosclerosis (AS). ADMA is increased in patients with chronic kidney disease (CKD), which is a predictor of early endothelial dysfunction in CKD and a serologic marker of AS. ADMA can directly lead to or indirectly promote AS, and the concentration of ADMA in vivo is relatively stable, not being easily influenced by other factors. So the prediction value of ADMA for AS and its adverse events in CKD patients is extremely high. ADMA can not only be used for early detection of AS but also be used for reflecting the effectiveness of early intervention and patients' response to treatment by monitoring its dynamic changes, helping in understanding the progress and predicting the prognosis of the disease. This paper reviews the causes of the increase of ADMA and its role in promoting the development of AS in CKD patients.

Correlation between serum asymmetric dimethylarginine and cystatin C in degenerative calcific aortic valvular disease and its clinical application value / 中国医师进修杂志

Objective@#To investigate the correlation between serum asymmetric dimethylarginine (ADMA) and cystatin C (CysC) in degenerative calcific aortic valvular disease and its clinical application value.@*Methods@#One hundred and eighty patients with degenerative calcific aortic valvular disease who were treated in Beijing Luhe Hospital Affiliated to Capital Medical University from June 2016 to June 2018 were selected as the study subjects, and another 82 healthy subjects from the same hospital in the same period were selected as the control group. Serum ADMA and CysC levels were detected by enzyme-linked immunosorbent assay and latex-enhanced immunoturbidimetric assay. Risk factors of degenerative calcific aortic valvular disease were analyzed by Logistic regression analysis. Evaluation of the diagnostic efficacy of serum ADMA and CysC for degenerative calcific aortic valvular disease was used by receiver operating characteristic curve.@*Results@#There were no significant differences in the general data between the two groups in terms of age, gender, body mass index, drinking history, smoking history, and history of hypertension (P>0.05). The systolic blood pressure(SBP), diastolic blood pressure (DBP), heart rate (HR), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterin(LDL-C), CysC and ADMA levels of the study group were significantly higher than those of the control group [(131.51 ± 19.09) mmHg (1 mmHg=0.133 kPa) vs. (126.48 ± 16.68) mmHg, (91.11 ± 16.35) mmHg vs. (86.89 ± 10.71) mmHg, (74.39 ± 15.22) beats/min vs. (70.09 ± 13.01) beats/min, (4.51 ± 1.12) mmol/L vs. (4.15 ± 0.92) mmol/L, (1.91 ± 0.63) mmol/L vs. (1.60 ± 0.65) mmol/L, (2.59 ± 1.13) mmol/L vs. (2.27 ± 0.85) mmol/L, (1.01 ± 0.22) mg/L vs. (0.79 ± 0.16) mg/L, (20.17 ± 6.38) ng/L vs. (11.88 ± 4.22) ng/L], and left ventricular ejection fraction (LVEF), high density lipoprotein cholesterin (HDL-C) levels were significantly lower than those of the control group [(56.45 ± 9.21)%vs. (60.87 ± 10.02)%, (1.56 ± 0.63) mmol/L vs. (1.76 ± 0.62) mmol/L], there were significant differences (P<0.05). Logistic multivariate regression analysis showed that serum CysC and ADMA were independent risk factors for degenerative calcific aortic valvular disease (P<0.05). Receiver operator characteristic (ROC) curve analysis showed that area under curve (AUC) of serum CysC for degenerative valvular heart disease was 0.785, with a sensitivity of 71.67%, and a specificity of 73.17%. The AUC of serum ADMA for degenerative valvular heart disease was 0.862, with a sensitivity of 71.67%, and a specificity of 87.80%. The AUC of serum CysC combined with ADMA in the diagnosis of degenerative valvular heart disease was 0.910, with a sensitivity of 85.56%, and a specificity of 84.15%, which was significantly higher than the two alone (Z=4.897 and 3.335, P<0.05).@*Conclusions@#Serum ADMA is positively correlated with CysC in patients with degenerative valvular heart disease, and can be used as diagnostic serum markers for degenerative calcific aortic valvular disease. It has clinical reference value for improving the diagnosis of degenerative calcific aortic valvular disease.

Correlation between serum asymmetric dimethylarginine and cystatin C in degenerative calcific aortic valvular disease and its clinical application value / 中国医师进修杂志

Objective To investigate the correlation between serum asymmetric dimethylarginine (ADMA) and cystatin C (CysC) in degenerative calcific aortic valvular disease and its clinical application value.Methods One hundred and eighty patients with degenerative calcific aortic valvular disease who were treated in Beijing Luhe Hospital Affiliated to Capital Medical University from June 2016 to June 2018 were selected as the study subjects,and another 82 healthy subjects from the same hospital in the same period were selected as the control group.Serum ADMA and CysC levels were detected by enzyme-linked immunosorbent assay and latex-enhanced immunoturbidimetric assay.Risk factors of degenerative calcific aortic valvular disease were analyzed by Logistic regression analysis.Evaluation of the diagnostic efficacy of serum ADMA and CysC for degenerative calcific aortic valvular disease was used by receiver operating characteristic curve.Results There were no significant differences in the general data between the two groups in terms of age,gender,body mass index,drinking history,smoking history,and history of hypertension (P＞ 0.05).The systolic blood pressure(SBP),diastolic blood pressure (DBP),heart rate (HR),total cholesterol (TC),triglyceride (TG),low density lipoprotein cholesterin(LDL-C),CysC and ADMA levels of the study group were significantly higher than those of the control group [(131.51 ± 19.09) mmHg (1 mmHg=0.133 kPa) vs.(126.48 ± 16.68) mmHg,(91.11 ± 16.35) mmHg vs.(86.89 ± 10.71) mmHg,(74.39 ± 15.22) beats/min vs.(70.09 ± 13.01)beats/min,(4.51 ± 1.12) mmol/L vs.(4.15 ± 0.92) mmol/L,(1.91 ± 0.63) mmol/L vs.(1.60 ± 0.65) mmol/L,(2.59 ± 1.13) mmol/L vs.(2.27 ± 0.85) mmol/L,(1.01 ± 0.22) mg/L vs.(0.79 ± 0.16) mg/L,(20.17 ± 6.38)ng/L vs.(11.88 ± 4.22) ng/L],and left ventricular ejection fraction (LVEF),high density lipoprotein cholesterin (HDL-C) levels were significantly lower than those of the control group [(56.45 ± 9.21)％vs.(60.87 ± 10.02)％,(1.56 ± 0.63) mmol/L vs.(1.76 ± 0.62) mmol/L],there were significant differences (P ＜ 0.05).Logistic multivariate regression analysis showed that serum CysC and ADMA were independent risk factors for degenerative calcific aortic valvular disease (P ＜ 0.05).Receiver operator characteristic (ROC) curve analysis showed that area under curve (AUC) of serum CysC for degenerative valvular heart disease was 0.785,with a sensitivity of 71.67％,and a specificity of 73.17％.The AUC of serum ADMA for degenerative valvular heart disease was 0.862,with a sensitivity of 71.67％,and a specificity of 87.80％.The AUC of serum CysC combined with ADMA in the diagnosis of degenerative valvular heart disease was 0.910,with a sensitivity of 85.56％,and a specificity of 84.15％,which was significantly higher than the two alone (Z =4.897 and 3.335,P ＜ 0.05).Conclusions Serum ADMA is positively correlated with CysC in patients with degenerative valvular heart disease,and can be used as diagnostic serum markers for degenerative calcific aortic valvular disease.It has clinical reference value for improving the diagnosis of degenerative calcific aortic valvular disease.

Factors Regulating Nitric Oxide Production in Spontaneously Hypertensive Rats Treated with Piper Sarmentosum Aqueous Extract

@#Introduction: Hypertension is a major risk factor for cardiovascular diseases which is one of the leading causes of death worldwide. Piper sarmentosum (PS) has been widely used in traditional medicine with proven antihypertensive and antioxidant effects. This study aims to evaluate the antihypertensive potential of PS aqueous extract (PSAE) and to investigate the factors modulating nitric oxide (NO) production through its anti-oxidant activities. Methods: PS leaves were extracted with distilled water, freeze-dried and examined to quantify their antioxidant activities through 2,2-diphenyl-1-picrylhydrazyl and ferric reducing ability plasma test. The antihypertensive effect of PSAE in spontaneous hypertensive rats (SHR) was evaluated using four different groups (n=6); C (negative control), K (PSAE 500mg/kg), P (3 mg/kg perindopril) and M (PSAE 500 mg/kg + 1.5 mg/kg perindopril). PSAE and other treatments were given via oral gavage for 28 days. The blood pressure (BP) was determined using the non-invasive BP monitoring tail cuff technique and recorded weekly. SHR’s blood was collected to determine the serum NO level using Griess assay. Asymmetric dimethylarginine (ADMA) and arginine levels were determined using high performance liquid chromatography. Results: The extract showed good in-vitro antioxidant activities and a significant reduction in both systolic and diastolic BP compared to control group. They were also a decrease in plasma ADMA and an increase in serum NO level. Meanwhile, arginine level does not change significantly. Conclusion: High in-vitro antioxidant activities in PSAE enhances the clearance of ADMA that leads to an increase in serum NO production hence ameliorating the blood pressure of SHR.

Asymmetric Dimethylarginine Predicts One-year Recurrent Cardiovascular Events: Potential Biomarker of "Toxin Syndrome" in Coronary Heart Disease / 中国结合医学杂志

OBJECTIVE@#To examine the prognostic value of serum levels of asymmetric dimethylarginine (ADMA) in patients with stable coronary heart disease (CHD) thus explore a potential biomarker of "toxin syndrome" in CHD.@*METHODS@#In this prospective nested case-control study, 36 of 1,503 Chinese patients with stable CHD experienced at least 1 recurrent cardiovascular event (RCE) during 1-year follow-up. Serum levels of ADMA at the start of follow-up were compared between these 36 cases and 36 controls which matched to cases in terms of gender, age, history of hypertension, and myocardial infarction.@*RESULTS@#Based on the crude model, subjects in the 2 highest ADMA quartiles showed significantly higher risk of developing RCE than those in the lowest ADMA quartile [odds ratio (OR) 4.09, 95% confidence interval (CI) 1.01 to 16.58; OR 6.76, 95% CI 1.57 to 29.07]. This association was also observed in the case-mix model (OR 5.51, 95% CI 1.23 to 24.61; OR 7.83, 95% CI 1.68 to 36.41) and multivariable model (OR 6.64, 95% CI 1.40 to 31.49: OR 13.14, 95% CI 2.28 to 75.71) after adjusting for confounders. The multivariable model which combined ADMA and high-sensitivity C-reactive protein (hsCRP) showed better predictive power with areas under the receiver operator characteristic curves (0.779) than the model of either ADMA (0.694) or hsCRP (0.636).@*CONCLUSION@#Serum ADMA level may be a potential biomarker of "toxin syndrome" in CHD which shows favorable prognostic value in predicting 1-year RCE in patients with stable CHD. [The registration number is ChiCTR-PRNRC-07000012].

Role of blood asymmetrical dimethylarginine levels in predicting ischemic stroke in patients with transient ischemic attack / 医学研究生学报

Objective Asymmetrical dimethylarginine (ADMA) levels have been associated with transient ischemic attack, however it is still difficult to define the effect of ADMA on the clinical result of TIA patients. This article aimed to investigate the effect of ADMA levels on ischemic stroke in TIA patients. Methods This study included 288 TIA patients treated in Department of Neurology in the Second Affiliated Hospital of Xi'an Medical College from January 2015 to December 2017. Blood ADMA was measured within 24 hours after patients’ admission. Patients were divided into low ADMA group (ADMA<0.62µmol/L, n=143) and high ADMA group (ADMA≥0.62µmol/L, n=145) according to the median blood ADMA level. The log-rank test was used to compare the survival rates of two groups. Multivariate Cox proportional hazards regression was used to analyze independent risk factors of ischemic stroke. Results In low ADMA group, 21 patients had ischemic stroke, and the stroke-free survival time was 18 (6-36) months. In high ADMA group, 32 patients had ischemic stroke, and the stroke-free survival time was 9 (3-33) months. There was a significant difference in the absence of stroke survival curves between the 2 groups (χ2=4.093, P=0.043). Multivariate Cox regression analysis showed that frequent TIA, high ABCD2 score, and high ADMA were independent risk factors for ischemic stroke. Conclusion Blood ADMA level is an important marker for predicting ischemic stroke in patients with TIA, which have certain significance for judging prognosis and guiding treatment.

Asymmetrical Dimethylarginine Levels in Hepatitis B Virus-Positive Patients

BACKGROUND: High asymmetrical dimethylarginine (ADMA) levels have been associated with endothelial dysfunction and contribute to the development of several diseases. However, data on the relationship between hepatitis B virus (HBV) and ADMA are limited. The aim of our study was to explore the relationship between ADMA and HBV by comparing the ADMA levels in patients with chronic active hepatitis B (CHB), inactive HBV carriers (carriers), and healthy volunteers (controls). METHODS: The participants were divided into three groups: 90 patients with CHB, 90 HBV carriers, and 90 controls. Serum ADMA levels were quantified using an ELISA kit (Cusabio, Wuhan, China). The data were analyzed using an ANOVA or the Kruskal-Wallis test as appropriate, with P<0.05 considered significant. RESULTS: Serum ADMA levels were significantly higher in patients with CHB (228.35±91.10 ng/mL) than in HBV carriers (207.80±75.80 ng/mL) and controls (207.61±89.10 ng/mL) (P=0.049). The clinical scores of the patients were positively correlated with ADMA levels. CONCLUSIONS: The elevated serum ADMA levels in patients with CHB confirm that HBV plays a role in vasculitis. Further investigation of the mechanisms contributing to the high levels of ADMA in CHB may contribute toward development of new treatment modalities.

The research progress of asymmetric dimethylarginine in chronic kidney disease / 医学研究生学报

Asymmetric dimethylarginine (ADMA) is a naturally occurring amino acid found in tissues and cells that circulates in plasma and is excreted in urine. As an inhibitor for nitric oxide synthases,ADMA produces considerable biological effects and severs as a risk marker of endothelial dysfunction and cardiovascular complications. Several recent lines of evidence suggest that ADMA has been associated with the progression of chronic kidney disease. Several potential mechanisms may be compromise of the integrity of the glomerular filtration barrier and development of renal fibrosis. In this review, we summary the existing literatures on the biology and physiology of ADMA on their associations with diseases,especially focusing on its role in the progression of chronic renal disease.

O papel dos genes DDAH1 e DDAH2 sobre o risco para desenvolvimento de disfunção erétil / The role of the DDAH1 and DDAH2 genes on the risk for developing erectile dysfunction

Uma das principais causas da disfunção erétil (DE) pode ser relacionada com o déficit de óxido nítrico (NO) no corpo humano. O principal componente para a produção do NO é o aminoácido L-arginina que é utilizado pelas enzimas óxido nítrico sintase neuronal (nNOS), endotelial (eNOS) e induzida (iNOS) para sua produção. A dimetilarginina assimétrica (ADMA) atua como inibidor endógeno dos três subtipos de NOS citadas acima e é metabolizada pelas enzimas dimetilarginina dimetilaminohidrolase 1 e 2 (DDAH1 e DDAH2). Diversos estudos têm relacionado a alteração na expressão ou atividade das enzimas DDAH bem como alterações em seus genes, com distúrbios onde a sinalização de NO é prejudicada. Os objetivos deste estudo foram investigar a associação de variantes genéticas dos genes DDAH1 (rs1554597 e rs18582) e DDAH2 (rs805304 e 805305) com a predisposição à disfunção erétil (DE), scores de função erétil e concentrações plasmáticas de nitrito e ADMA. Também verificar se estes marcadores bioquímicos estão relacionados aos scores de função erétil. Foram selecionados 130 pacientes com DE clínica e 98 participantes controles saudáveis sem DE. A função erétil dos voluntários foi avaliada através do questionário Índice Internacional de Função Erétil (IIEF). Os genótipos dos rs1554597, rs805304 e rs805305 foram obtidos através da técnica de reação em cadeia da polimerase (PCR) seguida de digestão enzimática, e do rs18582 apenas por técnica de PCR alelo específica. No grupo Pacientes, foram encontradas associações do gene DDAH1 com as concentrações plasmáticas de ADMA: o rs1554597 teve os genótipos TT e TC associados positivamente (TT: ? 0,13 e P = 0,008; TC: ? 0,09 e P = 0,016;) e o genótipo CC associado negativamente (? -0,22 e P <0,001); já o rs18582 teve o genótipo GG associado positivamente (? 0,22 e P <0,001) e o genótipo AA associado negativamente (? -0,16 e P = 0,001); o haplótipo TG foi associado positivamente (? 0,12 e P = 0,016) e o haplótipo CA negativamente (? -0,18 e P = 0,002). Com relação ao nitrito, associações dos haplótipos do gene DDAH2 foram encontradas, o haplótipo CC foi associado negativamente (? -0,03 e P = 0,045) e o haplótipo AG foi associado positivamente (? 0,03 e P = 0,045).O rs18582 teve o genótipo GG associado positivamente com as concentrações plasmáticas de nitrito, no modelo aditivo (? 0,15 e P = 0,009) e no modelo dominante (? 0,08 e P = 0,009), e os genótipos GA ou AA associados negativamente com as concentrações plasmáticas de nitrito, apenas no modelo dominante (? -0,08 e P = 0,009). Não foi encontrada nenhuma outra associação significativa no estudo

One of the main causes for erectile dysfunction (ED) is related to nitric oxide (NO) deficiency in human body. The main substrate for NO synthesis is the amino acid L-arginine, which is processed by NO synthases (NOS) from three subtypes for its production: neuronal (nNOS), endothelial (eNOS) and inducible (iNOS). Asymmetric Dimethylarginine (ADMA) acts as an endogenous inhibitor of the three subtypes of NOS and is metabolized by enzymes dimethylarginine dimethylaminohydrolase types 1 and 2 (DDAH1 and DDAH2). Several studies associate the altered expression or activity of DDAH enzymes, as well as their genes, with diseases with hampered NO signaling. The objectives of this study were to investigate the association of genetic variants of DDAH1 (rs1554597 and rs18582) and DDAH2 (rs805304 and 805305) with vulnerability to develop ED, with altered scores of erectile function and with altered plasma concentrations of nitrite and ADMA. We also investigated whether these biochemical markers associated with erectile function scores and ED risk. We selected 130 patients with clinical ED and 98 healthy controls without ED. Erectile function was assessed through the International Index for Erectile Function (IIEF) questionnaire. Genotypes for rs1554597, rs805304 and rs805305 were obtained with polymerase chain reaction (PCR) followed by enzyme restriction (RFLP), while rs18582 was determined using Allele-Specific oligonucleotide PCR (ASO-PCR). At patients group, we found association of variants in DDAH1 gene with plasma ADMA levels: TT and TC genotypes of rs1554597 were associated with increases in ADMA (TT: ? 0.13 e P = 0.008; TC: ? 0.09 e P = 0.016;), while CC genotype was associated with decreases in ADMA (? 0.22 e P <0.001); regarding rs18582, GG genotype associated with increases in ADMA (? 0.22 e P <0.001), while AA genotype associated negatively (? -0.16 e P = 0.001); besides, haplotype TG was also associated with ADMA increases (? 0.12 e P = 0.016), while CA haplotype associated negatively with ADMA levels (? -0.18 e P = 0.002). Regarding nitrite, associations of the haplotypes of the DDAH2 gene were found, the haplotype CC was negatively associated (? -0,03 and P = 0,045) and the haplotype AG was positively associated (? 0,03 and P = 0,045) .O rs18582 had the GG genotype positively associated with plasma nitrite concentrations in the additive model (? 0.15 and P = 0.009) and in the dominant model (? 0.08 and P = 0.009), and negatively associated genotypes GA or AA with plasma nitrite concentrations, only in the dominant model (? -0.08 and P = 0.009). We found no further significant associations in our study

Role of nitric oxide synthase inhibitor in the skeletal muscle contractile dysfunction of type 2 diabetic rats / 中国医师杂志

Objective To investigate the role of endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) in the contractile dysfunction of skeletal muscle in diabetic rats and on which the therapeutic effects of L-Arginine.Methods Type 2 diabetic rats were induced by high fat diet and a single intraperitoneal injection of streptozotocin (STZ,30 mg/kg),followed by high fat diet for 8 weeks.Specific twicth tension and specific tetanic tension of soleus (SOL) and extensor digitorum longus (EDL) isolated from control and diabetic rats were detected by electric stimulation to reflect contractile function of skeletal muscle.ADMA content of skeletal muscle was analyzed by enzyme linked immunosorbent assay (ELISA),and activities of dimethylarginie dimethylaminohydrolase (DDAH) and NOS,NO content were measured by colorimetry.The protein expression of ADMA synthetase protein arginine methyl transferase 1 (PRMT1) and ADMA hydrolase DDAH and NOS were determined detected by Western blotting.Oral glucose tolerance test and protein expressions of phosphorylated insulin receptor substrate 1 (p-IRS-1) and protein kinase B (p-Akt) as well as the membrane transportation of glucose transporter 4 (Glut4) were measured to reflect insulin resistance.Results In comparison with control rats,specific twicth tension and tetanic tension of SOL and EDL in diabetic rats were significantly decreased (P ＜ 0.01),indicating the contractile dysfunction.Increased ADMA content (P ＜ 0.05),decreased DDAH and NOS activities as well as NO content (P ＜ 0.01) in comparison with up-regulated protein expression of PRMT1 and down-regulated protein expression of DDAH,endothelial NOS (eNOS) and neuronal NOS (nNOS) (P ＜ 0.05) were observed in the skeletal muscle of diabetic rats compared to control rats,indicating that the pathway of PRMT1/ADMA/DDAH/ NOS/NO was disordered in the skeletal muscle of diabetic rats.Furthermore,the glucose tolerance,both IRS-1 and Akt protein phosphorylation as well as the membrane translocation of Glut4 were decreased (P ＜ 0.05),indicating the insulin resistance in diabetic rats.Treatment with L-Arginine for 8 weeks not only significantly improved the contractile dysfunction but also reversed the disorder of ADMA signaling pathway and insulin resistance in skeletal muscle of diabetic rats compared to untreated diabetic rats.Conclusions The accumulation of endogenous NOS inhibitor ADMA contributes to the contractile dysfunction of skeletal muscle in diabetic rats,the underlying mechanism may be related to insulin resistance.

Effect of OXC and VPA on EEG,Hcy and ADMA in adult patients with partial epilepsy / 国际检验医学杂志

Objective To investigate the effect of oxcarbazepine(OXC) and sodium valproate(VPA) on electroencephalogram(EEG) and peripheral blood levels of homocysteine(Hcy) and asymmetric dimethylarginine(ADMA) in adult patients with partial epilepsy.Methods From May.2014 to May.2015,a total of 100 patients with partial epilepsy were enrolled and randomly divided into treatment group(treated with OXC) and control group(treated with VPA),with 50 cases in each group.After treatment,changes of EEG indices,Hcy,ADMA,cognitive function and adverse reaction were analyzed.Results Before treatment,there was no significant difference of EEG indices between the two groups(P>0.05).After treatment,the incidence rates of α wave decreasing more than 0.5 Hz,increasing of θ wave and increasing of δ wave were significantly different(P0.05).After treatment,serum Hcy and ADMA levels were both significantly increased(P0.05).After treatment,MMSE score of treatment group was higher than that of control group(P<0.05).In treatment group,there were 1 case of skin rash and 2 cases of gastrointestinal discomfort,which were self-improved.In control group,there were 3 cases of dizziness,5 cases of skin rash and 1 case of gastrointestinal discomfort,which were self-improved.Conclusion The effects of OXC and VAP on peripheral blood levels of Hcy and ADMA could be similar,and compared with VAP,OXC could significantly improve cognitive function in patients with epilepsy.

Expression and significance of ADMA/NOS/NO/cGMP pathway in maternal-fetal interface of patients with preeclampsia / 中国免疫学杂志

Objective:To study the expression and significance of ADMA/NOS/NO/cGMP pathway in the maternal-fetal interface of patients with preeclampsia. Methods: 60 patients were selected and divided into severe preeclampsia group, mild preeclampsia group and gestational hypertensive group according to the disease condition, meanwhile 20 healthy pregnant women of singleton receiving cesarean section were chosen as control group. Levels of NO and cGMP in placenta of the four groups were detected and compared,and activities of total NOS in placenta were measured and compared. The expression of eNOS and iNOS in placental tissue was detected by immunohistochemistry SP method. High-performance liquid chromatography was used to detect the level of ADMA in HUVECs. Results:The levels of NO in placenta of severe and mild preclampsia groups were (7. 6±3. 6) and (11. 4±4. 3) μmol/g, which were statistically significantly lower than that in control group(P<0. 05). The levels of cGMP in placenta of severe and mild pre-clampsia groups were ( 3. 26 ± 0. 31 ) and ( 4. 53 ± 0. 42 ) pmol/g, which were aslo significantly lower than that in control group ( P<0. 05). In the four groups,the level of cGMP in placenta was positively correlated with the level of NO in placenta(r=0. 672). The activities of total NOS in placenta of severe and mild preeclampsia groups were (10. 4±3. 0)and (14. 8±1. 6)U/mg protein,which were statistically significantly lower than that in control group ( P<0. 05 ) . In placenta of the four groups, the activity of total NOS was positively correlated with the level of NO(r=0. 785). The expression of eNOS in placenta of severe and mild preeclampsia groups was statistically significantly lower than that in control group ( P<0. 05 ) , the expression of iNOS in severe preeclampsia group was significantly higher than that in the control group(P<0. 05). The levels of ADMA in HUVECs of severe preeclampsia group,mild pre-eclampsia group and gestational hypertensive group were statistically significantly higher than that in the control group(P<0. 05). The level of ADMA in HUVECs was negatively correlated with the level of NO in placenta of the four groups ( r=-0. 582 ) . Conclusion:ADMA/NOS/NO/cGMP pathway may play an important role in the pathogenesis of preeclampsia.

Role of endogenous nitric oxide synthase inhibitor in erectile dysfunction of diabetic rats / 中国病理生理杂志

AIM:To investigate the role of nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) in erectile dysfunction of diabetic rats.METHODS:Type 2 diabetic rat model was established by 4 weeks of high-fat diet plus a single intraperitoneal injection of streptozotocin and continued high-fat diet feeding for 8 weeks.Corpus cavernosum was isolated from the rats under anesthetization,and the endothelium-dependent relaxation response to acetylcholine (ACh) was tested in an organ chamber to reflect erectile function.The level of ADMA in serum was detected.The NOS activity,nitric oxide (NO) content and cyclic guanosine monophosphate (cGMP) content in corpus cavernosum were measured.The protein expression of ADMA-NOS-NO pathway-related molecules and phosphodiesteras 5 (PDES) in the corpus cavernosum was detected by Western blot.Superoxide dismutase activity and malondialdehyde content were analyzed to evaluate oxidative stress.RESULTS:Elevated blood glucose and lowered insulin sensitivity were observed in the diabetic rats,indicating that type 2 diabetic rat model was successfully established.Compared with control group,the relaxation response to ACh of corpus cavernosum from diabetic rats was significantly decreased,which was accompanied with the elevation of serum ADMA level and reduction of NOS activity,NO content and cGMP content in the corpus cavernosum.The protein expression of ADMA-generating enzyme protein arginine methyltransferase 1 was up-regulated,while ADMA-metabolic enzymes dimethylarginine dimethylaminohydrolases 1 and 2,and ADMA-targeting enzymes endothelial NOS and neuronal NOS were down-regulated.The protein expression of PDE5 was up-regulated,accompanied with an increase in oxidative stress in the corpus cavemosum of diabetic rats.Incubation of isolated corpus cavernosum from normal rats with NOS inhibitor ADMA induced the similar relaxation dysfunction of corpus cavemosum response to ACh and decreased NO and cGMP contents in diabetic rats.CONCLUSION:Elevated endogenous NOS inhibitor ADMA plays an important role in erectile dysfunction of diabetic rats.The underlying mechanism may be related to the reduction of NO production and the increase in oxidative stress.

Role of endogenous nitric oxide synthase inhibitor in erectile dysfunction of diabetic rats / 中国病理生理杂志

AIM:To investigate the role of nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) in erectile dysfunction of diabetic rats.METHODS:Type 2 diabetic rat model was established by 4 weeks of high-fat diet plus a single intraperitoneal injection of streptozotocin and continued high-fat diet feeding for 8 weeks.Corpus cavernosum was isolated from the rats under anesthetization,and the endothelium-dependent relaxation response to acetylcholine (ACh) was tested in an organ chamber to reflect erectile function.The level of ADMA in serum was detected.The NOS activity,nitric oxide (NO) content and cyclic guanosine monophosphate (cGMP) content in corpus cavernosum were measured.The protein expression of ADMA-NOS-NO pathway-related molecules and phosphodiesteras 5 (PDES) in the corpus cavernosum was detected by Western blot.Superoxide dismutase activity and malondialdehyde content were analyzed to evaluate oxidative stress.RESULTS:Elevated blood glucose and lowered insulin sensitivity were observed in the diabetic rats,indicating that type 2 diabetic rat model was successfully established.Compared with control group,the relaxation response to ACh of corpus cavernosum from diabetic rats was significantly decreased,which was accompanied with the elevation of serum ADMA level and reduction of NOS activity,NO content and cGMP content in the corpus cavernosum.The protein expression of ADMA-generating enzyme protein arginine methyltransferase 1 was up-regulated,while ADMA-metabolic enzymes dimethylarginine dimethylaminohydrolases 1 and 2,and ADMA-targeting enzymes endothelial NOS and neuronal NOS were down-regulated.The protein expression of PDE5 was up-regulated,accompanied with an increase in oxidative stress in the corpus cavemosum of diabetic rats.Incubation of isolated corpus cavernosum from normal rats with NOS inhibitor ADMA induced the similar relaxation dysfunction of corpus cavemosum response to ACh and decreased NO and cGMP contents in diabetic rats.CONCLUSION:Elevated endogenous NOS inhibitor ADMA plays an important role in erectile dysfunction of diabetic rats.The underlying mechanism may be related to the reduction of NO production and the increase in oxidative stress.

Dimetilarginina asimétrica plasmática en mujeres obesas y no obesas con síndrome de ovarios poliquísticos / Asymmetric plasma dimethylarginine in obese women and non-obese with polycystic ovarian syndrome

Objetivo: determinar las concentraciones plasmáticas de factor de dimetilarginina asimétrica (ADMA) en mujeres obesas y no obesas con diagnóstico de síndrome de ovarios poliquísticos (SOPQ). Métodos: se realizó un estudio de casos y controles en mujeres con diagnóstico de SOPQ y controles sanas de edades similares, con menstruaciones regulares y ovarios normales por ecografía y fueron divididas en cuatro grupos (grupo A: SOPQ obesas; grupo B: SOPQ no obesas; grupo C: controles obesas y grupo D controles no obesas) de acuerdo con el índice de masa corporal (obesas > 30 Kg/m2 y no obesas < 25 kg/m2 . Se midieron las concentraciones de hormonas sexuales, globulina fijadora de hormonas sexuales, glucosa sérica, insulina y ADMA. Resultados: las mujeres con SOPQ obesas y no obesas presentaron concentraciones más elevadas de hormonas sexuales e insulina comparadas con el grupo control de obesas y no obesas (p < 0,0001). Se observó que las mujeres con SOPQ presentaron concentraciones significativamente más altas de ADMA (grupo A: 0,56 +/- 0,05 picomol/L y grupo B: 0,51 +/- 0,03 picomol/L) comparado con los controles (grupo C: 0,47 +/- 0,02 picomol/L y grupo D 0,45 +/- 0,04 picomol/L; p < 0,0001). Se observó que las concentraciones de ADMA presentaban correlación positiva y significativa con los valores de glicemia e insulina en ayunas en las mujeres con SOPQ (p < 0,0001). Conclusión: Existen diferencias significativas en las concentraciones plasmáticas del ADMA entre las mujeres con SOPQ obesas y no obesas respecto a los controles normales.(AU)

Objective: To determine plasma concentrations of asymmetric dimethylarginine (ADMA) in obese and non-obese women with polycystic ovary syndrome (PCOS). Methods: A Case control study was done of women with diagnosis of PCOS and age-matched healthy controls, regular menstruations and normal ultrasound ovaries were selected Participants were divided in four groups (group A: PCOS and obese; group B: PCOS and non-obese; group C: obese controls and group D non-obese controls) according to body mass index (obese > 30 Kg/m2 y non-obese < 25 kg/m2 ). Concentrations of sexual hormones, sex hormone-binding globulin, serum glucose, insulin and ADMA. Results: Obese and non-obese women with PCOS had higher luteinizing hormone, follicle stimulating hormone, androstenodione, testosterone, and insulin levels as compared to women in the obese and non-obese control group, respectively (p < 0.0001). Women with PCOS had significantly higher of of ADMA (group A 0,56 +/- 0.05 picomol/L and group B: 0.51 +/- 0.03 picomol/L) as compared with controls (group C: 0.47 +/- 0.02 picomol/L and group D 0.45 +/- 0.04 picomol/L; p < 0.0001). We observed that ADMA concentrations presented a positive and significant correlation with fasting glycaemia and insulin in PCOS women (p < 0.0001). Conclusion: there are significant differences in plasma ADMA.(AU)

Células progenitoras endoteliais circulantes em crianças e adolescentes obesos / Circulating endothelial progenitor cells in obese children and adolescents

Resumo Objetivo Investigar a relação entre os números de células progenitoras endoteliais circulantes e a ativação endotelial em uma população pediátrica com obesidade. Métodos Estudo observacional e transversal, que incluiu 120 crianças e adolescentes com obesidade primária de ambos de sexos, entre seis e 17 anos, recrutados de nossa Clínica de Riscos Cardiovasculares. O grupo de controle contou com 41 crianças e adolescentes com índice de massa corporal normal. As variáveis analisadas foram: idade, sexo, índice de massa corporal, pressão arterial sistólica e diastólica, proteína C reativa de alta sensibilidade, perfil lipídico, leptina, adiponectina, resistência à insulina para avaliação do modelo de homeostase, proteína quimiotática de monócitos-1, E-seleticna, dimetilarginina assimétrica e números de células endoteliais progenitoras circulantes. Resultados A resistência à insulina foi correlacionada à dimetilarginina assimétrica (p = 0,340; p = 0,003), que foi diretamente correlacionada, porém de forma muita amena, à E-seleticna (ρ = 0,252; p = 0,046). Não constatamos que a proteína C reativa de alta sensibilidade estivesse correlacionada a marcadores de ativação endotelial. A pressão arterial sistólica foi diretamente correlacionada ao índice de massa corporal ρ = 0,471; p < 0,001) e à resistência à insulina para avaliação do modelo de homeostase (ρ = 0,230; p = 0,012) e inversamente correlacionada à adiponectina (ρ = −0,331; p < 0,001) e à lipoproteína de alta densidade-colesterol ρ = −0,319; p < 0,001). Os números de células progenitoras endoteliais circulantes foram diretamente correlacionados, porém de forma muito amena, ao índice de massa corporal (r = 0,211; p = 0,016), à leptina (ρ = 0,245; p = 0,006), aos níveis de triglicerídeos (r = 0,241; p = 0,031) e à E-seleticna ρ = 0,297; p = 0,004). Conclusão Os números de células progenitoras endoteliais circulantes são elevados em crianças e adolescentes obesos com comprovação de ativação endotelial. Isso sugere que, na infância, os mecanismos de reparação endotelial estão presentes no contexto da ativação endotelial.

Abstract Objective This study aimed to investigate the relationship between circulating endothelial progenitor cell count and endothelial activation in a pediatric population with obesity. Methods Observational and transversal study, including 120 children and adolescents with primary obesity of both sexes, aged 6-17 years, who were recruited at this Cardiovascular Risk Clinic. The control group was made up of 41 children and adolescents with normal body mass index. The variables analyzed were: age, gender, body mass index, systolic and diastolic blood pressure, high-sensitivity C-reactive protein, lipid profile, leptin, adiponectin, homeostasis model assessment-insulin resistance, monocyte chemoattractant protein-1, E-selectin, asymmetric dimethylarginine and circulating progenitor endothelial cell count. Results Insulin resistance was correlated to asymmetric dimethylarginine (ρ = 0.340; p = 0.003), which was directly, but weakly correlated to E-selectin (ρ = 0.252; p = 0.046). High sensitivity C-reactive protein was not found to be correlated to markers of endothelial activation. Systolic blood pressure was directly correlated to body mass index (ρ = 0.471; p < 0.001) and the homeostasis model assessment-insulin resistance (ρ = 0.230; p = 0.012), and inversely correlated to adiponectin (ρ = −0.331; p < 0.001) and high-density lipoprotein cholesterol (ρ = −0.319; p < 0.001). Circulating endothelial progenitor cell count was directly, but weakly correlated, to body mass index (r = 0.211; p = 0.016), leptin (ρ = 0.245; p = 0.006), triglyceride levels (r = 0.241; p = 0.031), and E-selectin (ρ = 0.297; p = 0.004). Conclusion Circulating endothelial progenitor cell count is elevated in obese children and adolescents with evidence of endothelial activation, suggesting that, during infancy, endothelial repairing mechanisms are present in the context of endothelial activation.

Relationship Between Plasma Level of Asymmetric Dimethylarginine and Coronary Artery Ectasia in Relevant Patients / 中国循环杂志

Objective: To investigate the relationship between plasma level of asymmetric dimethylarginine (ADMA) and coronary artery ectasia in relevant patients. Methods: A total of 72 patients received coronary angiography (CAG) in our hospital were studied and the patients were divided into 3 groups: Coronary ectasia group, Coronary stenosis group and Normal coronary group.n=24 in each group. Plasma levels of ADMA, symmetric dimethylarginine (SDMA) and L-arginine (Arg) were measured by HPLC-MS/MS methods. The relationship between ADMA and CAD was examined by Logistic regression analysis. Results: Plasma level of ADMA in Coronary ectasia group (0.437 ± 0.098) μmol/L and Coronary stenosis group (0.456 ± 0.088) μmol/L were higher than that in Normal coronary group (0.381 ± 0.057) μmol/L,P<0.05. The ratio of Arg/ADMA in Coronary ectasia group (208.54 ± 61.52) and Coronary stenosis group (220.00 ± 104.82) were lower than that in Normal coronary group (254.26 ± 76.22),P<0.05. Logistic regression analysis presented that with adjusted age, gender, smoking, family history of CAD and LDL-C level, and plasma ADMA was still related with CAD (Partial regression coefifcient 9.469, P=0.011). Conclusion: Plasma levels of ADMA were higher in patients with coronary artery ectasia/stenosis than those with normal coronary artery; while ADMA levels were similar between the patients with coronary ectasia and stenosis. Plasma ADMA level was the independent risk factor of CAD.