The relationship between reduced choroidal thickness due to high plasma asymmetrical dimethylarginine level and increased severity of diabetic retinopathy / Altos níveis de dimetil-arginina assimétrica no plasma podem aumentar a gravidade da retinopatia diabética através da redução da espessura da coroide

ABSTRACT Purpose: To evaluate the relationship between subfoveal choroidal thickness and plasma asymmetrical dimethylarginine level and the severity of diabetic retinopathy in patients with type 2 diabetes mellitus. Methods: A total of 68 cases, including 15 patients without diabetic retinopathy, 17 patients with nonproliferative diabetic retinopathy, 16 patients with type 2 diabetes mellitus and proliferative diabetic retinopathy, and 20 healthy patients (control group), were enrolled in this study. Subfoveal choroidal thickness was measured manually using the enhanced depth imaging optical coherence tomography scanning program, and plasma asymmetrical dimethylarginine level was measured using a commercial micro enzyme-linked immunosorbent assay kit. Results: The subfoveal choroidal thickness values and plasma asymmetrical dimethylarginine levels were significantly different between the four groups (p<0.001 and p<0.001). The subfoveal choroidal thickness values were significantly lower in the proliferative diabetic retinopathy group than in the other three groups (no diabetic retinopathy, nonproliferative diabetic retinopathy, and control groups; p<0.001, p=0.045, and p<0.001, respectively). The plasma asymmetrical dimethylarginine levels were significantly higher in the proliferative diabetic retinopathy group than in the other three groups (p<0.001, p<0.04, and p<0.001, respectively). In addition, a significant negative correlation was also found between plasma asymmetrical dimethylarginine level and subfoveal choroidal thickness (p<0.001, r=-0.479). Conclusion: Asymmetrical dimethylarginine is an important marker of endothelial dysfunction and endogenous endothelial nitric oxide synthase inhibitor. The severity of diabetic retinopathy was related to increased plasma asymmetrical dimethylarginine level and reduced subfoveal choroidal thickness in type 2 diabetic patients with diabetic retinopathy.

RESUMO Objetivo: Avaliar a relação da espessura subfoveal da coroide e dos níveis plasmáticos de dimetil-arginina assimétrica com a gravidade da retinopatia diabética em pacientes com diabetes mellitus tipo 2. Métodos: Foram incluídos 68 casos, compreendendo 15 pacientes sem retinopatia diabética, 17 pacientes com retinopatia diabética não proliferativa, 16 pacientes com retinopatia diabética proliferativa, e 20 casos saudáveis (grupo de controle). A espessura subfoveal da coroide foi medida manualmente, usando o programa de varredura com tomografia computadorizada óptica com imagem profunda aprimorada, e os níveis plasmáticos de dimetil-arginina assimétrica foram medidos usando um kit microELISA comercial. Resultados: Os valores da espessura subfoveal da coroide e os níveis plasmáticos de dimetil-arginina assimétrica foram significativamente diferentes nos quatro grupos (p<0,001 para ambos os parâmetros). Os valores da espessura subfoveal da coroide foram significativamente menores no grupo com retinopatia diabética proliferativa do que nos outros três grupos (sem retinopatia diabética, retinopatia diabética não proliferativa e grupo de controle, com p<0,001, p=0,045 e p<0,001, respectivamente). Já os níveis plasmáticos de dimetil-arginina assimétrica foram significativamente maiores no grupo com retinopatia diabética proliferativa do que nos outros três grupos (p<0,001, p=0,04 e p<0,001, respectivamente). Além disso, também foi encontrada uma correlação negativa significativa entre os níveis plasmáticos de dimetil-arginina assimétrica e a espessura subfoveal da coroide (p<0,001, r=-0,479). Conclusão: A dimetil-arginina assimétrica é um importante marcador de disfunção endotelial e um inibidor endógeno da óxido nítrico sintase. Foi encontrada uma relação da gravidade da retinopatia diabética e de níveis elevados de dimetil-arginina assimétrica no plasma com a redução da espessura subfoveal da coroide em pacientes diabéticos tipo 2 com retinopatia diabética.

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.

The effect of nitric oxide, endothelial nitric oxide synthetase, and asymmetric dimethylarginine in hemorrhoidal disease

SUMMARY AIM The aim of this study was to examine the roles of nitric oxide (NOx), endothelial nitric oxide synthetase (eNOS), and asymmetric dimethylarginine (ADMA), which is the major endogenous inhibitor of nitric oxide synthases (NOS), in the pathophysiology of hemorrhoidal disease. METHODS This study included 54 patients with grades 3 and 4 internal hemorrhoidal disease and 54 patients without the disease who attended the General Surgery Clinic. NOx, eNOS, and ADMA levels were measured with the Enzyme-Linked ImmunoSorbent Assay (ELISA) method. RESULTS The patients had higher NO and eNOS levels and lower ADMA levels than the control subjects (p<0.001). A significant highly positive correlation was found between NO and eNOS (p<0.001). Nevertheless, there was a highly negative correlation between ADMA and NO-eNOS(p<0.001, p<0.001). CONCLUSION This preliminary study reveals that higher NOx and eNOS activities and lower ADMA levels in the rectal mucosa are observed in patients with hemorrhoidal disease than in those with normal rectal tissue. The imbalance between endothelium-derived relaxing factors, such as NO and endogenous competitive inhibitor of NOS, ADMA, may cause hemorrhoidal disease. Our study proposes that hemorrhoids display apparent vascular dilatation and present with bleeding or swelling. ADMA is an effective NOS inhibitor and may be a promising therapeutic option for hemorrhoidal disease.

RESUMO OBJETIVO O objetivo deste estudo foi examinar os papéis do óxido nítrico (NOx), do óxido nítrico sintetase endotelial (eNOS) e da dimetilarginina assimétrica (ADMA), que é o principal inibidor endógeno das óxido nítrico sintase (NOS) na fisiopatologia da doença hemorróida. MÉTODOS Este estudo incluiu 54 pacientes com doença hemorróida interna de grau 3 e 4 e 54 pacientes sem a doença que se inscreveram na Clínica Geral de Cirurgia. Os níveis de NOx, eNOS e ADMA foram medidos com o método de Ensaio Imuno absorvente ligado a enzima (ELISA). RESULTADOS Os pacientes têm níveis mais altos de NO e eNOS e níveis mais baixos de ADMA do que os indivíduos controle (p <0,001). Uma correlação altamente positiva significativa foi encontrada entre o NO-eNOS (p <0,001). No entanto, houve uma correlação negativa muito séria entre ADMA e NO-eNOS (p <0,001, p <0,001). CONCLUSÃO Este estudo preliminar revela que os pacientes com doença hemorróida têm atividades mais altas de NOx e eNOS e níveis mais baixos de ADMA na mucosa retal do que os pacientes com tecido retal normal. Desequilíbrio entre o fator relaxante derivado do endotélio, como; O NO e o inibidor competitivo endógeno da NOS, ADMA, podem causar doenças hemorróidas. Nosso estudo propõe que as hemorróidas exibam aparente dilatação vascular e apresentam sangramento ou inchaço, a ADMA é um inibidor eficaz da NOS e pode ser uma opção terapêutica promissora para a doença hemorróida.

Visceral adiposity index and triglyceride/high-density lipoprotein cholesterol ratio in hypogonadism

ABSTRACT Background Cardiometabolic risk is high in patients with hypogonadism. Visceral adiposity index (VAI) and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio are the practical markers of atherosclerosis and insulin resistance and independent predictors of cardiaovascular risk. To date, no study has evaluated VAI levels and TG/HDL-C ratio in hypogonadism. Subjects and methods A total of 112 patients with congenital hypogonadotrophic hypogonadism (CHH) (mean age, 21.7 ± 2.06 years) and 124 healthy subjects (mean age, 21.5 ± 1.27 years) were enrolled. The demographic parameters, VAI, TG/HDL-C ratio, asymmetric dimethylarginine (ADMA), high-sensitivity C-reactive protein (hs-CRP), and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured for all participants. Results The patients had higher total cholesterol (p = 0.04), waist circumference, triglycerides, insulin, and HOMA-IR levels (p = 0.001 for all) than the healthy subjects. VAI and ADMA and TG/HDL-C levels were also higher in patients than in healthy subjects (p < 0.001 for all). VAI was weakly correlated with ADMA (r = 0.27, p = 0.015), HOMA-IR (r = 0.22, p = 0.006), hs-CRP (r = 0.19, p = 0.04), and total testosterone (r = −0.21, p = 0.009) levels, whereas TG/HDL-C ratio was weakly correlated weakly with ADMA (r = 0.30, p = 0.003), HOMA-IR (r = 0.22, p = 0.006), and total testosterone (r = −0.16, p = 0.03) levels. Neither VAI nor TG/HDL-C ratio determined ADMA, HOMA-IR, and hs-CRP levels. Conclusions The results of this study demonstrate that patients with hypogonadism have elevated VAI and TG/HDL-C ratio. These values are significantly correlated with the surrogate markers of endothelial dysfunction, inflammation, and insulin resistance. However, the predictive roles of VAI and TG/HDL-C ratio are not significant. Prospective follow-up studies are warranted to clarify the role of VAI and TG/HDL-C ratio in predicting cardiometabolic risk in patients with hypogonadism.

Nitric oxide and asymmetric dimethyl arginine (ADMA) levels in an experimental hydronephrotic kidney caused by unilateral partial ureteral obstruction

ABSTRACT Aim Our aim is to measure asymmetric dimethyl arginine and nitric oxide levels in rats with induced unilateral acute ureteral obstruction to research the effects on the kidney. Material and Methods The study included 21 adolescent (average age 6 weeks) Sprague-Dawley male rats weighing between 240-290g divided at random into 3 groups. Group-1: Control group (n=6): underwent no procedures. Group-2: Sham group (n=6): underwent the same procedures as the experimental group without ureter and psoas muscle dissection. Group-3: Group with induced partial unilateral ureteral obstruction (n=9). All rats were sacrificed after 12 weeks. Superoxide dismutase enzyme activity and nitrite and nitrate salt levels were measured in renal tissue. Plasma nitrite-nitrate and ADMA levels were examined. Results In the experimental group histopathological changes observed included renal pelvis dilatation, flattened papillae, sclerotic glomerulus and fibrosis. In the experimental group tissue SOD and blood ADMA levels were higher than the control and sham groups (p<0.05) while tissue NO and plasma NO values were lower than in the sham and control groups (p<0.05). Conclusion Oxidative stress and disruption of NO synthesis play an important role in renal function and histopathological changes after obstructive renal disease. To prevent renal complications developing after obstructive nephropathy we believe that a new strategy may be research on reducing ADMA.

The relationship between serum asymmetric dimethylarginine levels and subjective sleep quality in normotensive patients with type 2 diabetes mellitus

BACKGROUND/AIMS: Poor sleep quality (SQ) is associated with increased cardiovascular mortality and morbidity. Additionally, asymmetric dimethylarginine (ADMA) is an independent predictor of cardiovascular mortality and morbidity. However, no sufficient data regarding the relationship between ADMA levels and SQ have been reported. The goal of the current study was to evaluate the association between SQ and ADMA levels in normotensive patients with type 2 diabetes mellitus. METHODS: The study participants consisted of 78 normotensive type 2 diabetics. The SQ of all participants was assessed using the Pittsburgh Sleep Quality Index (PSQI). Patients with a global PSQI score > 5 were defined as "poor sleepers." Factors associated with poor SQ were analyzed using a multiple regression model. Serum ADMA levels were measured using high performance liquid chromatography. RESULTS: The median ADMA levels of the poor sleepers were increased compared with patients defined as good sleepers (5.5 [4.2 to 6.6] vs. 4.4 [2.9 to 5.4], p < 0.01, respectively). However, the L-arginine/ADMA ratio was decreased in poor sleepers (p < 0.01). Global PSQI scores were positively correlated with ADMA levels (p < 0.01) and negatively correlated with the L-arginine/ADMA ratio (p = 0.02). ADMA levels were correlated with sleep latency (p < 0.01) and sleep efficiency (p = 0.01). Logistic regression analysis showed that ADMA levels (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.16 to 2.44; p = 0.01) and body mass index (OR, 1.15; 95% CI, 1.01 to 1.31; p = 0.04) were associated with poor SQ independently of glomerular filtration rate, sex, age, duration of diabetes, hemoglobin A1c, total cholesterol, and systolic blood pressure. CONCLUSIONS: Self-reported SQ was independently associated with ADMA levels in normotensive patients with diabetes mellitus.

Óxido nítrico e arginina di-metil assimétrica: possível via de explicação para o trabalho de parto pré-termo / Nitric oxide and asymmetric dimethyl arginine: a novel pathway to explain preterm labor

O trabalho de parto pré-termo (TPPT) assim como as outras causas de prematuridade respondem pela maior parcela da mortalidade e morbidade neonatal no mundo. Várias vias metabólicas já foram estudadas e diversas alterações já foram encontradas em pacientes que desenvolve TPPT. A via metabólica do óxido nítrico (NO) é reconhecida como um dos possíveis mecanismos de desencadeamento fisiopatológico do TPPT. Níveis elevados de dimetil-arginina assimétrica (ADMA), substância endógena inibidora da NO sintetase, estão relacionados com o desencadeamento de TPPT e com maiores taxas de complicações neonatais. O presente estudo aborda as evidências sobre a relação do TPPT e ADMA e as possíveis aplicações clínicas dessa associação.(AU)

Pre-term labor (PTL), as well as the other causes of prematurity, account for the largest portion of neonatal mortality and morbidity in the world. Several metabolic pathways were studied and a significative number of impairments have already been found in patients who develop PTL. The metabolic pathway of nitric oxide (NO) is recognized as one of the possible mechanisms of pathophysiological PTL?s trigger. High levels of asymmetric dimethyl arginine (ADMA), endogenous inhibitory substance of NO synthetase, are related to the triggering of PTL and with higher rates of neonatal complications. The present study addresses the evidence on the relationship of PTL and ADMA and possible clinical applications of this association.(AU)

Investigation of anti-cancer effects of cherry in vitro

Cherry [Prunus Cerasus] is still one of the most popular preserve in Turkish cuisine. Cherry has been traditionally used for the treatment of inflammatory-related symptoms. Recent researches have proved that cherry is a valuable natural source of some important bioactive compounds in human health preservation. Evidence suggests that, cherry consumption may decrease the risk of chronic diseases and cancer. The aim of the present study was to determine the effects of cherry on breast cancer cells lines, asymmetric dimethylarginine [ADMA] level and certain multidrugresistant bacteria. The cancer cell proliferation activity and analysis of apoptotic-necrotic cells was evaluated by using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide [MTT] and scoring of apoptotic cell nuclei. Measurement of ADMA and the minimum inhibitory concentration was accomplished by HPLC and the micro dilution broth method. The results showed that, extracts of cherry exhibit anti-proliferative activity in mammary adenocarcinoma [MCF-7] and mouse mammary tumor cell [4T1] breast cancer cells lines as well as induction of apoptosis, lower ADMA concentrations in cell cultures treated with cherry extract and antibacterial effects against certain multidrug-resistant bacteria in vitro. These findings may open new horizons for traditional anti-inflammatory product as prophylactictherapeutic agent from cancer, cardiovascular diseases and multidrug-resistant infections.

High plasma concentrations of asymmetric dimethylarginine inhibit ischemic cardioprotection in hypercholesterolemic rats

A low concentration of nitric oxide associated with a high concentration of asymmetric dimethylarginine (ADMA) can explain the lack of ischemic cardioprotection observed in the presence of hypercholesterolemia. The objective of the present study was to evaluate the effect of hypercholesterolemia on ischemic pre- and postconditioning and its correlation with plasma concentrations of ADMA. Male Wistar rats (6-8 weeks old) fed a 2% cholesterol diet (n = 21) for 8 weeks were compared to controls (n = 25) and were subjected to experimental myocardial infarction and reperfusion, with ischemic pre- and postconditioning. Total cholesterol and ADMA were measured in plasma before the experimental infarct and the infarct area was quantified. Weight, total cholesterol and plasma ADMA (means ± SE; 1.20 ± 0.06, 1.27 ± 0.08 and 1.20 ± 0.08 vs 0.97 ± 0.04, 0.93 ± 0.05 and 0.97 ± 0.04 µM) were higher in animals on the hypercholesterolemic diet than in controls, respectively. Cardioprotection did not reduce infarct size in the hypercholesterolemic animals (pre: 13.55% and post: 8% compared to 7.95% observed in the group subjected only to ischemia and reperfusion), whereas infarct size was reduced in the animals on a normocholesterolemic diet (pre: 8.25% and post: 6.10% compared to 12.31%). Hypercholesterolemia elevated ADMA and eliminated the cardioprotective effects of ischemic pre- and postconditioning in rats.

[Inhibitory effect of asymmetric dimethylarginine and NG-Monomethyl-L-arginine methyl ester on nitric oxide synthase activity]

Nitric oxide synthase [NOS] paly a role in nitric oxide [NO] generation. Despite the beneficial effects of NO on different body systems its overproduction of produce reactive nitrogen species [RNS] and nitrosilation of proteins. This study was done to evaluate the effect of asymmetric dimethylarginine [ADMA] and NG-Monomethyl-L-arginine methyl ester [L-NMMA] on inhibition of nitric oxide synthase activity. In this laboratory study, Nitric oxide synthase was extracted from 500 grams of sheep kidney by homogenization, ammonium sulphate precipitation and column chromatography on DEAE-32 Cellulose and 2', 5'-ADP-agarose. During purification, protein content was measured according to the Bradford and enzyme activity was assayed using the Griess reactions the inhibitory effects of 25 micro concentrations of ADMA and L-NMMA on purified enzyme were determined. Specific activity and yield of NOS were 0.6 units/mg protein and 0.9%, respectively. Molecular weight of purified enzyme was 54 KD with SDS-PAGE. ADMA and L-NMMA in 25 micro concentrations reduced enzyme activity by 76 and 61.2%, respectively. Km values for NOS in absence and in presence of ADMA and L-NMMA were 5.32 microM, 31.25 microM [P<0.05] and 14.29 microM [P<0.05], respectively. Vmax for NOS in absence and presence of inhibitors was not changed. ADMA and L-NMMA have competitive inhibitory effect on NOS activity and ADMA have higher inhibitory effect than L-NMMA

Propolis attenuates oxidative injury in brain and lung of nitric oxide synthase inhibited rats

The blocking of nitric oxide synthase [NOS] activity may reason vasoconstriction with formation of reactive oxygen species. Propolis has biological and pharmacological properties, such as antioxidant. The aim of this study was to examine the antioxidant effects of propolis which natural product on biochemical parameters in brain and lung tissues of acute nitric oxide synthase inhibited rats by Nco-nitro-L-arginine methyl ester [L-NAME]. Rats have been received L-NAME [40 mg/kg, intraperitoneally], NOS inhibitor for 15 days to produce hypertension and propolis [200mg/kg, by gavage] the lastest 5 of 15 days. There were the increase [P0<001] in the malondialdehyde levels in the L-NAME treatment groups when compared to control rats, but the decrease [P<001] in the catalase activities in both brain and lung tissues. There were statistically changes [P<001] in these parameters of L-NAME+propolis treated rats as compared with E-NAME-treated group. The application of L-NAME to the Wistar rats resulted in well developed oxidative stress. Also, propolis may influence endothelial NO production. Identification of such compounds and characterisation of their cellular actions may increase our knowledge of the regulation of endothelial NO production and could provide valuable clues for the prevention or treatment of hypertensive diseases and oxidative stress

Asymmetric dimethylarginine [ADMA]: an emerging contributor to endothelial dysfunction in hyperthyroidism

Cardiovascular manifestations are frequent findings in patients with hyperthyroidism. Nitric oxide [NO], a key regulator of endothelial function, is synthesized from L-arginine by nitric oxide synthase [NOS]. Evidence has accumulated that asymmetric dimethylarginine [ADMA] is an endogenous competitive inhibitor of NOS. To measure plasma L-arginine and dimethylarginines [ADMA and SDMA] in patients with hyperthyroidism in order to assess their contribution to endothelial dysfunction and their relationship to plasma NO. The study was conducted on 50 newly diagnosed patients with overt hyperthyroidism as well as 30 age and sex matcned healthy controls. Plasma L-arginine, ADMA and SDMA were analyzed by HPLC. Plasma NO was measured by a colorimetric method based on Griess reagent. L-arginine, ADMA and SDMA were significantly increased, while NO and L-arginine/ADMA ratio were significantly decreased in hyperthyroid patients compared to controls. Serum freeT4 and free T3 were negatively correlated with plasma NO and L-arginine/ADMA ratio and positively correlated with L-arginine, ADMA and SDMA. Moreover, NO was significantly negatively correlated with each of the L-arginine and ADMA and significantly positively correlated with T.arginine/ADMA ratio. Results provide evidence of the presence of endothelial dysfunction in hyperthyroidism. The decrease in NO, and the increase in ADMA emphasizes that ADMA is an emerging contributor of endothelial dysfunction in hyperthyroidism

Cardiovascular disease markers in women with polycystic ovary syndrome with emphasis on asymmetric dimethylarginine and homocysteine

Polycystic ovary syndrome [PCOS] is a disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. Little is known about cardiovascular risk factors in patients with PCOS. We investigated plasma markers of cardiovascular disease in Saudi women with PCOS, with an emphasis on asymmetric dimethylarginine [ADMA] and total homocysteine [tHcy]. Fifty Saudi women with PCOS diagnosed by the Rotterdam criteria [mean age [SD] 30.2 [3.0] years] and 40 controls without PCOS [mean age 29.3 [2.5] years] had measyrements taken of clinical, metabolic, and hormonal parameters, including plasma ADMA, tHcy, lipoprotein [a] [[Lp[a]], and serum high sensitivity C-reactive protein [hs-CRP], nitric oxid, and fibrinogen. Insulin resistance was calculated by the homeostasis model assessment [HOMA-IR]. Women with PCOS had significantly higher fasting insulin, HOMA-IR, and luteinizing hormone [LH] levels than healthy controls [P<.001]. Lipid profile, free androgen index [FAI], ADMA, tHcy, hsCRP, and Lp[a] were significantly higher in women with PCOS compared with healthy controls [P<.001]. The women with PCOS had significantly lower nitric oxide and high-density lipoprotein cholesterol [HDL-C] levels compared with healthy controls [P<.001]. Our study revealed that Saudi women with PCOS had a significantly different levels of plasma markers of cardiovascular disease compared with normal controls. Therefore, clinicians who manage women with PCOS should follow up on these markers to reduce the risk of cardiovascular disease

Serum asymmetric dimethyl arginine [ADMA], nitric oxide [NO] and homocystine [HCY] levels in behcet's disease as biomarkers of endothelial cell dysfunction

To measure the serum levels of asymmetric dimethyl arginine [ADMA], nitric oxide [NO] and homocystine [Hcy] in patients with Behcet's disease as markers of endothelial cell dysfunction and to explain their role [s] in the disease pathogenesis and activity. This study included 14 male patients with Behcet's's disease and 10 age and sex matched healthy volunteers. Patients were divided into two groups: mucocutaneous and vasculitis groups. CBC, deferential leucocytic counts, ESR, CRP were performed as a guide for disease activity. ADMA, NO and homocystine, was measured in the serum of all studied groups by ELISA. Duplex ultrasono graphics of venous and arterial system were done for vasculitis group. There was significant increase in ADMA level in BD patients [0.918 +/- 0.240 micro mol/L] than control group [0.0.401 +/- 0.070 micro mol/L] with increase in vasculitis group [1.133 +/- 0.223 micro mol/L] than mucocutaneous group [0.756 +/- 0.049 micro mol/L]. The study reported significant decrease in NO level in BD patients [11.986 +/- 1.815 micro mol] than the control group [14.560 +/- 1.897 micro mol/L] with significant decrease in vasculitis group [10.333 than +/- 0.647 micro mol/L] than mucocutaneous group [13.225 +/- 1.312 micro mol/L]. There was also significant increase in Hey level in BD patients [25.271 +/- 4.980 micro mol/L] than control group [10.020 +/- 1.060 micro mol/L] with significant increase in vasculitis group [30.53 3 +/- 1.141 micro mol/L] than mucocuteneous group [21.325 +/- 1.896 micro mol/L. Increased ADMA with decrease NO and increase Hcy serum levels may be responsible for endothelial damage in BD and can be used as markers for endothelial cell dysfunction

Study of some biochemical and genetic risk factors for a therosclerosis in systemic lupus erythematososus patients

The aim of this study was to evaluate the relation between asymmetric dimethylarginine [ADMA], high sensitive C-reactive protein [hs-CRP], monocyte chemoattractant protein-1 [MCP-1] [both serum levels and the genotypes of the MCP-1 A-2518G polymorphism] with the development of carotid atherosclerosis in systemic lupus erythematosus patients [SLE]. Thirty non menopause SLE female patients and twenty healthy age-matched females were included. Both cases and controls were subjected to evaluation of body mass index [BMI], intimal-medial thickness [IMT], fasting blood sugar [FBS], serum lipids. Serum ADMA, hs-CRP, and MCP-1, levels were measured by ELISA. MCP-1 polymorphism was detected by PCR-RFLP. Our results showed that values foi IMT, hs-CRP, ADMA and MCP-1, were significantly higher in SLE patients than in healthy control with more significant increase in SLE patients with IMT >/= 1 mm than those with IMT <1 mm. Carotid IMT was significantly positively correlated with all the studied variables except for age, BMI and FBS, but significantly negatively correlated with HDL-C in all SLE patients. Genotype of MCP-1 [A-25 1 8G] showed that; GIG genotype was more frequent in SLE patients than controls. IMT, hs-CRP, ADMA and MCP-l from patients with G/G phenotypes were markedly higher than patients with the A/A or A/G genotype. In multiple regression analysis, ADMA and MCP-1 were the strongest independent determinants of IMT in SLE patients. In conclusion assessment of high levels of ADMA, hs-CRP, MPC-1, in addition to the MCP-l G allele may play a role in the pathogenesis of accelerated atherosclerosis in SLE patients and would be useful in identifying the risk of developing atherosclerosis

Asymmetric dimethylarginine (ADMA) and endothelial dysfunction: implications for atherogenesis: [review]

Atherosclerotic coronary heart disease is the leading cause of morbidity and mortality in industrialized countries, and endothelial dysfunction is considered a precursor phenomenon. The nitric oxide produced by the endothelium under the action of endothelial nitric oxide synthase has important antiatherogenic functions. Its reduced bioavailabilty is the beginning of the atherosclerotic process. The addition of two methyl radicals to arginine, through the action of methyltransferase nuclear proteins, produces asymmetric dimethylarginine, which competes with L-arginine and promotes a reduction in nitric oxide formation in the vascular wall. The asymmetric dimethylarginine, which is itself considered a mediator of the vascular effects of the several risk factors for atherosclerosis, can be eliminated by renal excretion or by the enzymatic action of the dimethylarginine dimethylaminohydrolases. Several basic science and clinical research studies suggest that the increase in asymmetric dimethylarginine occurs in the context of chronic renal insufficiency, dyslipidemia, high blood pressure, diabetes mellitus, and hyperhomocysteinemy, as well as with other conditions. Therapeutic measures to combat atherosclerosis may reverse these asymmetric dimethylarginine effects or at least reduce the concentration of this chemical in the blood. Such an effect can be achieved with competitor molecules or by increasing the expression or activity of its degradation enzyme. Studies are in development to establish the true role of asymmetric dimethylarginine as a marker and mediator of atherosclerosis, with possible therapeutic applications. The main aspects of the formation and degradation of asymmetric dimethylarginine and its implication in the atherogenic process will be addressed in this article.

Relationship between asymmetric dimethylarginine [ADMA] and endothelial dysfunction in chronic renal failure patients

The aim of this study was to assess serum asymmetric dimethylarginine [ADMA]and their relation to endothelial dysfunction in chronic renal failure [CRF] patients. A total of 50 CRF patients were divided to 2 groups [25 CRF patients on conservative treatment with glomerular filtration rate [GFR] 41.04 +/- 10.5 ml/min/1.73 m[2], and 25 patients on regular hemodialysis [HD], in addition to 20 healthy controls were studied. GFR was estimated by Cockroft-Gault formula. ADMA was measured by an enzyme- linked immunosorbent assay. Endothelial dysfunction was measured by flow-mediated dilatation [FMD] in brachial artery using high-resolution ultrasound. In addition, C-reactive protein [C-RP], serum albumin, total protein, total cholesterol, low density lipoprotein cholesterol [LDL-C], high density lipoprotein cholesterol [HDL-C], triglyceride and 24-h urinary proteins were performed. Compared with controls, CRF patients on conservative treatment as well as HD patients had higher levels of serum ADMA, brachial artery FMD was significantly lower among CRF patients on conservative treatment and HD patients, suggesting greater endothelial dysfunction, when CRF patients on conservative treatment were compared with HD patients, those HD patients had higher ADMA levels. Moreover, Serum ADMA levels did not change significantly after 4-hour dialysis in HD patients. In multivariate correlation, serum ADMA levels were correlated and independent predictor of FMD. serum ADMA levels were increased in CRF patients on conservative therapy and HD patients, and may be one of the contributing factors for the development of endothelial dysfunction in these patients

Relationship between asymmetric dimethylarginine [ADMA], proteinuria and endothelial dysfunction in chronic kidney disease

The aim of this study was to assess serum asymmetric dimethylarginine [ADMA] and their relation to endothelial dysfunction in chronic kidney disease [CKD] Patients with proteinuria. A total of 54 CKD Patients with normal glomerular filtration rate [GFR] were divided into three groups based on their urinary protein excretion in 24 h: 23 patients with nonnephrotic proteinuria [< 3.5 g/d], 17 patients with nephritic-range proteinuria, 14 patients with nephrotic-range proteinuria and secondary amyloidosis [SA] by renal biopsy, in addition to 18 healthy controls. Renal function was estimated with the Cockroft-Gault formula. ADMA was measured by high-performance liquid chromatography [HPLC], assessment of endothelial dysfunction by measuring flow-mediated dilatation [FMD] in brachial artery using high-resolution ultrasound. In addition, high sensitivity C-reactive protein [hsCRP], total cholesterol, triglycerides, high density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL-C], serum albumin and insulin resistance were performed for all patients. The proteinuric patients had higher levels of serum ADMA. hsCRP and insulin resistance. Compared with controls, brachial artery FMD was significantly lower among proteinuric patients, suggesting greater endothelial dysfunction. When patients with secondary amyloidosis were compared with patients with glomerulonephritis who had similar levels of proteinuria, those with amyloidosis had higher ADMA levels and lower FMD measurements. Even after adjusting for confounders, ADMA level correlated with both proteinuria and the presence of secondary amyloidosis, and was an independent predictor of FMD. In conclusion, serum ADMA concentrations were increased in CKD, especially in secondary amyloidosis, and this may explain part of the mechanism by which proteinuria increases cardiovascular morbidity and mortality

Different Regulation of Atrial ANP Release through Neuropeptide Y2 and Y4 Receptors

Neuropeptide Y (NPY) receptors are present in cardiac membranes. However, its physiological roles in the heart are not clear. The aim of this study was to define the direct effects of pancreatic polypeptide (PP) on atrial dynamics and atrial natriuretic peptide (ANP) release in perfused beating atria. Pancreatic polypeptides, a NPY Y4 receptor agonist, decreased atrial contractility but was not dose-dependent. The ANP release was stimulated by PP in a dose-dependent manner. GR 23118, a NPY Y4 receptor agonist, also increased the ANP release and the potency was greater than PP. In contrast, peptide YY (3-36) (PYY), an NPY Y2 receptor agonist, suppressed the release of ANP with positive inotropy. NPY, an agonist for Y1, 2, 5 receptor, did not cause any significant changes. The pretreatment of NPY (18-36), an antagonist for NPY Y3 receptor, markedly attenuated the stimulation of ANP release by PP but did not affect the suppression of ANP release by PYY. BIIE0246, an antagonist for NPY Y2 receptor, attenuated the suppression of ANP release by PYY. The responsiveness of atrial contractility to PP or PYY was not affected by either of the antagonists. These results suggest that NPY Y4 and Y2 receptor differently regulate the release of atrial ANP.