cysteinylglycine and Cardiovascular-Diseases

The aim of our study was to investigate the effects of carbamazepine (CBZ) and oxcarbazepine (OXCBZ) on aminothiol levels, including homocysteine (Hcy), cysteine, and cysteinylglycine, in chronically treated patients.. Epileptic patients receiving CBZ or OXCBZ were recruited as part of routine clinical practice. Demographic data and concomitant medications were recorded from the patient medical file.. Sixty patients were included in the study; 30 patients were treated with CBZ and 30 with OXCBZ. Median Hcy level was significantly higher in CBZ-treated patients (20.6 micromol/l) than in OXCBZ-treated patients (14.0 micromol/l, p < 0.0001). No correlation was evidenced between antiepileptic drugs or metabolite levels and Hcy levels for each group.. Less change observed with OXCBZ compared with CBZ on aminothiol levels could constitute an advantage for OXCBZ treatment in patients with other factors influencing Hcy levels and/or at high risk for cardiovascular diseases.

Topics: Adolescent; Adult; Anticonvulsants; Carbamazepine; Cardiovascular Diseases; Cysteine; Dipeptides; Epilepsy; Female; Homocysteine; Humans; Male; Middle Aged; Oxcarbazepine; Risk Factors

Metformin treatment increases circulating homocysteine levels. We studied whether administration of folate reduces serum total homocysteine levels in patients on long-term metformin treatment.. A prospective, randomized, double-blind, placebo-controlled study lasting for 12 weeks and taking place in a university hospital setting.. Thirty patients treated with a metformin dose of at least 1000 mg day-1 for a minimum of 1 year were included. At baseline serum total homocysteine levels were within the reference range. One patient who withdrew and one who died were excluded from the statistical evaluation. Twenty-six of the remaining patients suffered from NIDDM, the other two from hyperlipidaemia.. Patients were randomized into two groups at week 0. The folate group received 0.25 mg day-1 of folate in addition to 60 mg day-1 of Fe2+, while the placebo group received only 60 mg day-1 of Fe2+.. Fasting homocysteine, cysteine, cysteinylglycine, vitamin B12 and folate were measured at week 0, 4 and 12. Changes from week 0 to week 4 and from week 0 to week 12 were calculated.. Folate administration reduced serum levels of total homocysteine in the folate group as compared with the placebo group by 13.9% (P < 0.01) and 21.7% (P < 0.001) at week 4 and 12, respectively. In the folate group versus the placebo group serum levels of vitamin B12 increased by 9.9% (P = 0.010) and 9.6% (P = 0.043) while folate levels increased by 96.9 and 89.9% at week 4 and 12, respectively.. The present study indicates that the homocysteine-increasing effect of metformin can be counteracted by folate administration.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dipeptides; Double-Blind Method; Female; Folic Acid; Hematinics; Homocysteine; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Prospective Studies; Risk Factors; Time Factors; Treatment Outcome; Vitamin B 12

Serum thiols have shown associations with surrogate markers of cardiovascular disease. However, little information is available on their combined association with validated cardiovascular risk scores for primary prevention at population level. We sought to determine whether individual serum thiol concentrations and substrate/product ratios within the transsulfuration pathway are independently associated with such scores.. Data on clinical and demographic characteristics, serum thiols (homocysteine, cysteine, taurine, glutamylcysteine, total glutathione and cysteinylglycine) and high-sensitivity C-reactive protein (CRP) were collected from a sample of the Hunter Community Study without previous cardiovascular events [n=350, median age (IQR) = 62 (59-66) years]. Five-year absolute cardiovascular risk score for each subject was calculated using the Framingham Risk Equation.. Median risk score was 7% (IQR 4-10). After adjusting for body mass index, estimated glomerular filtration rate and physical activity regression analysis showed independent associations between cardiovascular risk scores and a) higher serum homocysteine (B 0.066, 95% CI 0.040 to 0.091, P<0.001) and lower cysteine (B -0.003, 95% CI -0.005 to -0.001, P=0.003) and glutathione (B -0.029, 95% CI -0.056 to -0.003, P=0.03) concentrations; and b) higher homocysteine/cysteine (B 0.114, 95% CI 0.066 to 0.161, P<0.001) and lower glutathione/cysteinylglycine (B -1.145, 95% CI -2.030 to -0.260, P=0.011) ratios. No significant associations were observed between cardiovascular risk scores, taurine and CRP.. Serum homocysteine, cysteine and glutathione are independently associated with cardiovascular risk scores at population level. Enzymatic pathways involved in reduced bioconversion of homocysteine into cysteine and increased glutathione degradation might play an important role in such associations.

Topics: Aged; Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Cysteine; Dipeptides; Female; Glomerular Filtration Rate; Glutathione; Homocysteine; Humans; Male; Middle Aged; Regression Analysis; Risk Assessment; Sulfhydryl Compounds; Sulfur; Taurine

Serum homocysteine, when studied singly, has been reported to be positively associated both with the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine [ADMA, via inhibition of dimethylarginine dimethylaminohydrolase (DDAH) activity] and with symmetric dimethylarginine (SDMA). We investigated combined associations between transsulfuration pathway thiols, including homocysteine, and serum ADMA and SDMA concentrations at population level.. Data on clinical and demographic characteristics, medication exposure, C-reactive protein, serum ADMA and SDMA (LC-MS/MS), and thiols (homocysteine, cysteine, taurine, glutamylcysteine, total glutathione, and cysteinylglycine; capillary electrophoresis) were collected from a sample of the Hunter Community Study on human ageing [n = 498, median age (IQR) = 64 (60-70) years].. REGRESSION ANALYSIS SHOWED THAT: a) age (P = 0.001), gender (P = 0.03), lower estimated glomerular filtration rate (eGFR, P = 0.08), body mass index (P = 0.008), treatment with beta-blockers (P = 0.03), homocysteine (P = 0.02), and glutamylcysteine (P = 0.003) were independently associated with higher ADMA concentrations; and b) age (P = 0.001), absence of diabetes (P = 0.001), lower body mass index (P = 0.01), lower eGFR (P<0.001), cysteine (P = 0.007), and glutamylcysteine (P < 0.001) were independently associated with higher SDMA concentrations. No significant associations were observed between methylated arginines and either glutathione or taurine concentrations.. After adjusting for clinical, demographic, biochemical, and pharmacological confounders the combined assessment of transsulfuration pathway thiols shows that glutamylcysteine has the strongest and positive independent associations with ADMA and SDMA. Whether this reflects a direct effect of glutamylcysteine on DDAH activity (for ADMA) and/or cationic amino acid transport requires further investigations.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Aging; Amidohydrolases; Arginine; Australia; C-Reactive Protein; Cardiovascular Diseases; Cohort Studies; Community Medicine; Cysteine; Dipeptides; Female; Glutathione; Homocysteine; Humans; Male; Middle Aged; Taurine

We hypothesized that redox analysis could provide sensitive markers of the oxidative pathway associated to the presence of an increasing number of cardiovascular risk factors (RFs), independently of type. We classified 304 subjects without cardiovascular disease into 4 groups according to the total number of RFs (smoking, hypertension, hypercholesterolaemia, hyperhomocysteinaemia, diabetes, obesity, and their combination). Oxidative stress was evaluated by measuring plasma total and reduced homocysteine, cysteine (Cys), glutathione, cysteinylglycine, blood reduced glutathione, and malondialdehyde. Twenty-seven percent of subjects were in group 0 RF, 26% in 1 RF, 31% in 2 RF, and 16% in ≥ 3 RF. By multivariable ordinal regression analysis, plasma total Cys was associated to a higher number of RF (OR = 1.068; 95% CI = 1.027-1.110, P = 0.002). Total RF burden is associated with increased total Cys levels. These findings support a prooxidant effect of Cys in conjunction with RF burden, and shed light on the pathophysiologic role of redox state unbalance in preclinical atherosclerosis.

Topics: Adult; Analysis of Variance; Cardiovascular Diseases; Cysteine; Diabetes Complications; Dipeptides; Female; Glutathione; Humans; Hypercholesterolemia; Hyperhomocysteinemia; Hypertension; Logistic Models; Male; Malondialdehyde; Middle Aged; Obesity; Oxidation-Reduction; Oxidative Stress; Prospective Studies; Risk Assessment; Risk Factors; Smoking