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Plasma Levels of Asymmetric Dimethylarginine and Total Homocysteine in First Degree Relatives of Type 2 Diabetic Patients
Trakya Universitesi Tip Fakultesi Dergisi , 2007,
Abstract: Objectives: Cardiovascular diseases are more common among first degree relatives of type 2 diabetic patients than healthy subjects without a family history of diabetes. Plasma asymmetric dimethylarginine (ADMA) and homocysteine (Hcy) levels are markers of endothelial dysfunction and cardiovascular disease. The objective of this study was to evaluate levels of ADMA, Hcy and their association with cardiovascular risk factors in first degree relatives of type 2 diabetic patients.Patients and Methods: The circulating ADMA and Hcy levels were measured in 15 first degree relatives of type 2 diabetic patients and 15 control subjects without a known family history of diabetes.Results: No statistically significant differences were found in plasma levels of ADMA and Hcy between the two groups (p>0.05). Plasma ADMA levels correlated significantly with waist circumference (p=0.02), fasting insulin levels (p=0.03), insulin resistance (p=0.01), total cholesterol (p=0.04) and HDL-cholesterol (p=0.03) levels in the first degree relatives of type 2 diabetic patients.Conclusion: These results suggest that plasma ADMA levels do not directly contribute to the development of endothelial dysfunction in first degree relatives of type 2 diabetic patients with cardiovascular risk factors.
Cardiovascular disease markers in women with polycystic ovary syndrome with emphasis on asymmetric dimethylarginine and homocysteine
Mohamadin Ahmed,Habib Fawzia,Al-Saggaf Abdulrahman
Annals of Saudi Medicine , 2010,
Abstract: Background and Objectives :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). Patients and Methods : 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). Results : 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). Conclusion : 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 Dimethylarginine, Nitrate, Vitamin B12, and Homocysteine Levels in Individuals with Pulmonary Embolism  [PDF]
Murat Altunta?,Figen Atalay,Murat Can,Remzi Alt?n,Meltem Tor
Mediators of Inflammation , 2011, DOI: 10.1155/2011/215057
Abstract: We aimed to analyze the pre- and posttreatment serum asymmetric dimethylarginine (ADMA), nitrate (NO3), vitamin B12 and homocysteine levels in pulmonary embolism (PTE) patients and to determine the prognostic value of these variables in predicting chronic thromboembolic pulmonary hypertension (CTEPH). This study was conducted in 64 patients. The patients were classified into the two groups: patients with normal pulmonary artery pressure (PAP) (group I) and patients with high PAP with persistent lung perfusion defects or who died at the end of 3 months of therapy (group II). We found statistically significant differences between two groups with respect to the partial oxygen pressure, the oxygen saturation, and the PAP, but there was no difference between the two groups with respect to the pretreatment ADMA, NO3, or homocysteine levels. The vitamin B12 levels were higher in group II. The NO3 levels increased and the ADMA and vitamin B12 levels decreased with treatment in both groups. These results suggest that these parameters are not predictive of the development of CTEPH. 1. Introduction A pulmonary artery embolism is defined as a partial or complete occlusion of a pulmonary arterial branch. Approximately 70% of cases are caused by pelvic or leg thromboses [1, 2]. Precise figures for the incidence of pulmonary embolism (PTE) are not available. The annual incidence of diagnosed venous thromboembolism (VTE) is 150 to 200 cases per 100,000 population [3]. Considering the unknown number of clinically silent embolisms and the nonspecific clinical presentation, the actual disease frequency is underestimated. PTE is a severe and potentially fatal disease when the embolism is massive. CTEPH, which develops after the obliteration of the pulmonary vascular bed by repeated and organized PTE, is one of the less frequently seen forms of PTE and is characterized by unexplained dyspnea and a reduction in exercise capacity [4]. CTEPH is defined as symptomatic pulmonary hypertension (mean pulmonary artery pressure (mPAP) >25?mmHg) with persistent lung perfusion defects [5]. CTEPH is a life threatening and debilitating disease affecting up to 5% of survivors of PTE [6]. The disease is underdiagnosed, and its true prevalence is still unclear. It is characterized by intraluminal thrombus organization and fibrotic stenoses or complete obliteration of the pulmonary arteries. Pulmonary embolism, either as single or recurrent episode(s), is believed to be the initiating event, followed by progressive vascular remodeling [7]. CTEPH is a common variation of PTE [8]. Endothelial
Relation of asymmetric dimethylarginine levels with conventional risk score systems in the healthy subjects with positive family history for coronary artery disease  [cached]
Hulusi Sat?lm??o?lu,Hakan ?zhan,Sinan Albayrak,Ahmet Kaya
Anadolu Kardiyoloji Dergisi , 2011,
Abstract: Objective: Coronary artery disease is the most common cause of death in Turkey and the world. Asymmetric dimethylarginine is the major inhibitor of nitric oxide synthesis in humans. It has been shown that increased levels of asymmetric dimethylarginine is associated with endothelial dysfunction and increased atherogenesis. In this study, we aimed to investigate whether asymmetric dimethylarginine level is related with conventional risk score systems in subjects who had family history of coronary artery disease. Methods: Fifty two subjects within 20-40 years old of whom first degree relatives had myocardial infarction at young ages and 26 age and sex matched control subjects were included in this cross-sectional observational study. Frequency of diabetes, hyperlipidemia, smoking and serum levels of homocysteine, high-sensitive C-reactive protein (hsCRP) and asymmetric dimethylarginine were compared between risk group and control subjects. Relation of asymmetric dimethylarginine level with Framingham and TEKHARF risk scores was also compared. Chi-square and Mann-Whitney U tests were used to compare categorical and continuous variables, respectively.Results: Fasting serum glucose, triglyceride, high-density lipoprotein, diastolic blood pressure, waist circumference and TEKHARF scores were increased in the subjects who had family history of myocardial infarction. Total cholesterol, low-density lipoprotein, hsCRP, homocysteine, creatinine and Framingham risk score were similar in studied groups . Asymmetric dimethylarginine levels were 0.1μmol/L higher in the risk group; however this difference could not reach significance (0.7±0.1 μmol/l vs 0.8±0.1 μmol/l; p=0.061). Conclusion: Measurement of serum asymmetric dimethylarginine levels did not reveal utility in defining conventional coronary artery disease risk score systems in cases that had positive family history. Larger studies including patients with different risk tertiles are needed.
Risk of Dementia Associated with Elevated Plasma Homocysteine in a Latin American Population  [PDF]
Inara J. Chacón,Aldrín E. Molero,Gloria Pino-Ramírez,José A. Luchsinger,Joseph H. Lee,Gladys E. Maestre
International Journal of Alzheimer's Disease , 2009, DOI: 10.4061/2009/632489
Abstract: The relationship between total homocysteine (tHcy) and dementia risk remains controversial, as the association varies among populations and dementia subtypes. We studied a Venezuelan population that has high prevalence of both elevated tHcy and dementia. We tested the hypotheses that (1) elevated tHcy is associated with increased dementia risk, (2) the risk is greater for vascular dementia (VaD) than for Alzheimer's disease (AD), and (3) a history of stroke may partly explain this association. 2100 participants (≥55 years old) of the Maracaibo Aging Study underwent standardized neurological, neuropsychiatric, and cardiovascular assessments. Elevated tHcy was significantly associated with dementia, primarily VaD. When history of stroke and other confounding factors were taken into account, elevated tHcy remained a significant risk factor in older (>66 years), but not in younger (55–66 years) subjects. Ongoing studies of this population may provide insight into the mechanism by which tHcy increases risk for dementia.
Asymmetric dimethylarginine (ADMA) and endothelial dysfunction: implications for atherogenesis
Landim, Maurício Batista Paes;Casella Filho, Ant?nio;Chagas, Ant?nio Carlos Palandri;
Clinics , 2009, DOI: 10.1590/S1807-59322009000500015
Abstract: 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.
Plasma Homocysteine, Folate and B12 Vitamin Levels in Alzheimer Disease, Vascular Dementia and Mild Cognitive Impairment  [cached]
Journal of Neurological Sciences , 2006,
Abstract: Purpose: Elevated plasma total homocysteine(Hcy) concentrations are associated with Alzheimer’s disease(AD) and vascular dementia(VaD). The purpose of this study is to examine the association of dementia with blood levels of Hcy, and its biological determinants folate and vitamin B12.Methods: The studied groups of 28 cerebro vascular disease(CVD) patients, 22 VaD patients, 51 AD patients, 20 mild cognitive impairment (MCI) and 25 healthy elderly subjects. These patients and control subjects were studied for Hcy, vitamin B12, and folate.Results: All patients and control subjects were compared for age, sex, educational level, and Hcy, folate and Vit.B12 levels. Hcy was significantly increased in VaD patients (mean ±.SD= 17.8±5.5 μmol/L) and AD patients (mean ±.SD=14.2±3.1 μmol/L. p<0.001) as compared to controls (mean ±.SD=9.9±2.1 μmol/L); AD patients also showed increased levels of Hcy. Folate levels were significantly reduced in both VaD (mean ±.SD=8.8±2.9 ng/ml) and AD (mean ±.SD=9.7±3.1 ng/ml; p<0.001) patients, vitamin B12 showed significantly reduced levels in VaD (mean ±.SD=230.53±22.1 pg/ml) and AD patients (mean ±.SD=285.92±22.8 pg/m). No significant relationship was observed between MCI and control subjects for folate, vitamin B12,and Hcy levels.Conclusion: Further large-scale prospective trials are required to assess whether lowering plasma Hcy levels prevent AD or delay progression of clinical symptoms of AD.
Alev Ero?lu Alt?nova,Metin Arslan
Marmara Medical Journal , 2009,
Abstract: Asymmetric dimethylarginine (ADMA) is the major inhibitor of nitric oxide biosynthesis in human. In recent reports, elevated plasma ADMA levels have been demonstrated to be associated with endothelial dysfunction and increased atherogenesis. Elevated ADMA levels, which contribute to the increased cardiovascular risk, have been determined in several endocrine diseases. The role of ADMA in various endocrine diseases such as diabetes mellitus, obesity and thyroid dysfunction will be discussed in this review.
Assessment of Endothelial Dysfunction: The Role of Symmetrical Dimethylarginine and Proinflammatory Markers in Chronic Kidney Disease and Renal Transplant Recipients  [PDF]
Lidija Memon,Vesna Spasojevic-Kalimanovska,Natasa Bogavac-Stanojevic,Jelena Kotur-Stevuljevic,Sanja Simic-Ogrizovic,Vojislav Giga,Violeta Dopsaj,Zorana Jelic-Ivanovic,Slavica Spasic
Disease Markers , 2013, DOI: 10.1155/2013/306908
Abstract: Objectives. The study was designed to evaluate associations between symmetric dimethylarginine (SDMA), inflammation, and superoxide anion ( ) with endothelial function and to determine their potential for screening of endothelial dysfunction in patients with chronic kidney disease (CKD) and renal transplant (RT) recipients. Materials and Methods. We included 64 CKD and 52 RT patients. Patients were stratified according to brachial artery flow-mediated dilation (FMD). Results. Logistic regression analysis showed that high SDMA and high sensitive C-reactive protein (hs-CRP) were associated with impaired FMD in CKD and RT patients, after adjustment for glomerular filtration rate. The ability of inflammation, SDMA, and to detect impaired FMD was investigated by receiving operative characteristic analysis. Hs-CRP (area under the curves (AUC) = 0.754, ), IL-6 (AUC = 0.699, ), and SDMA (AUC = 0.689, ) had the highest ability to detect impaired FMD. SDMA in combination with inflammatory parameters and/or had better screening performance than SDMA alone. Conclusions. Our results indicate a strong predictable association between hs-CRP, SDMA, and endothelial dysfunction in CKD patients and RT recipients. The individual marker that showed the strongest discriminative ability for endothelial dysfunction is hs-CRP, but its usefulness as a discriminatory marker for efficient diagnosis of endothelial dysfunction should be examined in prospective studies. 1. Introduction Patients with chronic kidney disease (CKD) are at high risk of developing cardiovascular disease. In addition, renal transplant (RT) recipients are 10 times more likely to suffer from fatal cardiac events compared with the general population [1]. Many risk factors, traditional and nontraditional, are involved in the pathogenesis of atherosclerosis in these patients. Endothelial dysfunction, oxidative stress, and inflammation are recognised as new risk factors in CKD patients. Nevertheless, interplay between these factors remains largely unexplored. Impairment of endothelium-dependent vasodilatation has largely been attributed to reduced availability or biological activity of nitric oxide (NO). NO is synthesized from L-arginine in a reaction catalysed by NO synthase (NOS). Methionine is metabolised to homocysteine by a demethylation pathway. The final result of this pathway is the formation of asymmetric dimethyl-L-arginine (ADMA), an NOS inhibitor. Increased ADMA may limit intracellular L-arginine availability for NO synthesis or inhibit NOS. In addition, homocysteine mediates superoxide anion ( )
Asymmetric dimethylarginine, NO and collateral growth  [cached]
Sinan Altan Kocaman
Anadolu Kardiyoloji Dergisi , 2009,
Abstract: Atherosclerosis is a chronic inflammatory disease, which selectively involves the arteries in the vascular system. Atherosclerosis develops because of reactions occurring in vessel wall beginning with response to endothelial injury. Endothelial dysfunction is characterized with impairment and loss of monolayer cells covering the inside of the vessels, which is endothelium. Endothelial dysfunction is the first stage in atherosclerosis. Coronary angiogenesis and collateral growth are chronic adaptations to myocardial ischemia to restore coronary blood flow and salvage myocardium in the ischemic region. Nitric oxide (NO) which represents the status of endothelial health plays a major role in collateral vessel development. Asymmetric dimethylarginine (ADMA) which is endogenous inhibitor of NO synthesis may impair the effective coronary collateral vessel development. Increased plasma ADMA levels are related with poor coronary collateral development. ADMA may be responsible for the difference in coronary collateral vessel development among similar patients with coronary artery disease. Nitric oxide inhibitors have a determinative relation with endothelial cell functions which may be integral prerequisite in all steps of collateral development. The aim of this review is to evaluate the interrelations between ADMA and collateral growth.
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