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Elevated asymmetric dimethylarginine (ADMA) concentrations predict cardiovascular events in patients with type 2 diabetes mellitus (T2DM). It has been shown that alpha-lipoic acid (ALA) improves endothelial function and oxidative stress [...]

Tetrahydrobiopterin corrects Escherichia coli endotoxin-induced endothelial dysfunction. Mittermayer F, Pleiner J, Schaller G, et al. Am J Physiol Heart Circ Phvsiol 2005 Jun 17:[Epub ahead of print]. Acute inflammation causes [...]

Elevated asymmetric dimethylarginine (ADMA) concentrations predict cardiovascular events in patients with type 2 diabetes mellitus (T2DM). It has been shown that alpha-lipoic acid (ALA) improves endothelial function and oxidative stress in these patients. The present study investigated if ALA reduces ADMA in patients with T2DM. Plasma concentrations of ADMA, L-arginine and symmetric dimethylarginine (SDMA) were determined in a double-blind, randomized, placebo-controlled study in patients with T2DM. Intravenous ALA (n = 16) or placebo (n = 14) was administered daily for 3 weeks. ALA reduced ADMA while no change was observed with placebo (mean change -0.05 micromol/1[95% CI: -0.01; -0.09] vs. 0.01 micromol/1 [95% CI: -0.05; -0.03]; ANOVA p = 0.031). SDMA and L-arginine were not affected by ALA. In conclusion ALA treatment reduces ADMA in patients with T2DM. Long-term studies need to demonstrate if ALA may cause cardiovascular risk reduction. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Systemic inflammation causes vasodilation and impairs the vascular response to catecholamines. There is evidence that altered vasoreactivity is associated with increased production of free radicals. We studied the influence of systemic doses of the antioxidant N-acetylcysteine on inflammatory cytokines and renal plasma flow and on the systemic pressor response to norepinephrine during experimental endotoxemia. DESIGN: A double-blind, placebo-controlled crossover study. SETTING: Medical University of Vienna, Clinical Pharmacology, Vienna General Hospital, AKH. SUBJECTS: Eight healthy, male humans. INTERVENTIONS: Intravenous administration of Escherichia coli endotoxin (lipopolysaccharide, 20 IU/kg) on two separate study days with concomitant intravenous infusion of placebo or N-acetylcysteine (150 mg/kg loading dose; 15 mg/kg/hr continuous infusion), respectively. MEASUREMENTS AND MAIN RESULTS: Measurements of inflammatory cytokines, of renal plasma flow by the para-aminohippurate-clearance method, and of the systemic pressor response to norepinephrine were taken at baseline and after endotoxin. Lipopolysaccharide increased body temperature and plasma concentrations of tumor necrosis factor-alpha, which was mitigated during N-acetylcysteine infusions. Likewise, the lipopolysaccharide-induced increases in renal plasma flow and decreases in blood pressure were attenuated, and the hyporeactivity of pulse rate to norepinephrine 4 hrs after lipopolysaccharide was improved by N-acetylcysteine. CONCLUSION: High doses of N-acetylcysteine might exert protective effects on systemic hemodynamics and on the reactivity to catecholamines in humans challenged by lipopolysaccharide. This action of the antioxidant N-acetylcysteine is paralleled by humoral anti-inflammatory mechanisms and may be useful in patients with systemic inflammation. [ABSTRACT FROM AUTHOR]

Objective: Hyperdynamic circulation and systemic vasodilation complicate cirrhosis of the liver and are related to vasoconstrictor hyporeactivity. We investigated whether impaired vasoconstrictor responsiveness may be overcome by antioxidants in patients with decompensated alcoholic cirrhosis.Design: Controlled clinical study.Setting: University setting.Patients: Nine patients with liver cirrhosis Child-Pugh grade C and nine healthy age-matched volunteers.Interventions: Forearm blood flow responses to intra-arterial norepinephrine, angiotensin II, and the nitric oxide synthase inhibitor N-monomethyl-l-arginine were measured by strain-gauge plethysmography and compared between groups of patients. To assess the role of oxidative stress, the antioxidant vitamin C (24 mg/min) was administered locally into the brachial artery, and forearm blood flow responses were reassessed.Measurements and Main Results: Plasma concentrations of vitamin C were lower in patients with cirrhosis (p < .05). In patients with cirrhosis, the reactivity to norepinephrine and angiotensin II was markedly reduced (p < .05 vs. controls). Coadministration of vitamin C completely restored the potency of vasoconstrictors to that in controls but had no effect in healthy subjects. No changes were observed in time-control experiments in cirrhosis patients (n = 3) employing vehicle coinfusion. The response to N-monomethyl-L-arginine was comparable between groups and not affected by vitamin C.Conclusions: Oxidative stress with consumption of antioxidants seems to play an important role in the development of vasoconstrictor hyporeactivity in patients with cirrhosis. Antioxidant therapy may be a promising clinical approach to restore vasoconstrictor hyporeactivity in these patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Oral ingestion of proteins or amino acids is associated with endothelial dysfunction. The effect of commercial amino acid peritoneal dialysis solutions on vascular function is unknown. OBJECTIVE: We compared the acute effect of intraperitoneal amino acid administration with that of intraperitoneal glucose administration on vascular function in peritoneal dialysis patients. DESIGN: In an open-label randomized, controlled, crossover and observer-blinded trial, we examined the acute effect of an intraperitoneal application of 2 L commercial 1.1% amino acid solution compared with that of a 2.27% glucose solution in 13 peritoneal dialysis patients. The primary endpoint was the change in forearm reactive hyperemia 6 h after instillation of either dialysis solution. RESULTS: After 6 h of dwell time, reactive hyperemia was substantially impaired after administration of the amino acid solution compared with the glucose solution (median difference: 202%; 95% CI: 57%, 368%; P = 0.007). In a comparison of differences between values at 6 h and those before treatment, reactive hyperemia significantly decreased during the dwell with the amino acid dialysis solution compared with that with the glucose dialysis solution (median difference: 242%; 95% CI: 53%, -457%; P = 0.013). In an analysis of smoking and nonsmoking patients separately, the difference in forearm blood flow between the 2 treatments was still statistically significant. CONCLUSIONS: One 6-h dwell with a commercial amino acid dialysis solution acutely impairs forearm reactive hyperemia in smoking and nonsmoking peritoneal dialysis patients. Because endothelial dysfunction is associated with increased morbidity and mortality, the long-term use of these solutions may increase the risk of cardiovascular disease. Copyright © 2003 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Neuromuscular electrical stimulation (NMES) is a frequently applied therapy for the treatment of pain and a therapeutic option to increase thigh muscle strength and endurance capacity in patients with heart failure. Electromagnetic interference (EMI) by the signals with sensing of ICDs is possible. Eight patients with subpectoral ICD systems and different transvenous bipolar sensing leads were subjected to electrical stimulation of the neck and shoulder and of the thighs using different stimulation algorithms. EMI with ventricular sensing was detectable in three of eight subjects. EMI occurred during stimulation of the neck (n = 2) and thigh (n = 2). EMI by NMES with atrial sensing was seen in two of four subjects with dual chamber ICDs. The safety of peripheral NMES has to be individually tested as EMI can also occur in ICD patients with bipolar sensing. [ABSTRACT FROM AUTHOR]

Journal of Human Hypertension (2002) 16, 875–877. doi:10.1038/sj.jhh.1001491 [ABSTRACT FROM AUTHOR]

Abstract Background New-onset diabetes mellitus after transplantation (NODAT), a frequent and serious complication after transplantation, is associated with decreased graft and patient survival. Currently, it is diagnosed and treated primarily according to existing guidelines for type II diabetes. To date, only a few trials have studied antidiabetic drugs in patients with NODAT. Vildagliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor that improves pancreatic islet function by enhancing both α- and β-cell responsiveness to increased blood glucose. Experimental data show potential protective effects of DPP-4 inhibitors on islet function after exogenous stress stimuli including immunosuppressants. Therefore, the therapy of NODAT with this class of compounds seems attractive. At present, vildagliptin is used to treat type II diabetes as monotherapy or in combination with other antidiabetic drugs, since that it efficiently decreases glycated hemoglobin (HbA1c) values. Additionally, vildagliptin has been shown to be safe in patients with moderately impaired kidney function. This study will evaluate the safety and efficacy of vildagliptin monotherapy in renal transplant recipients with recently diagnosed NODAT. Methods/Design This study is a randomized, placebo-controlled, double-blind, prospective phase II trial. Using the results of routinely performed oral glucose tolerance tests (OGTT) in stable renal transplant patients at our center, we will recruit patients without a history of diabetes and a 2 h glucose value surpassing 200 mg/dl (11.1 mmol/l). They are randomized to receive either 50 mg vildagliptin or placebo once daily. A total of 32 patients with newly diagnosed NODAT will be included. The primary endpoint is the difference in the 2 h glucose value between baseline and the repeated OGTT performed 3 months after treatment start, compared between the vildagliptin- and the placebo-group. Secondary endpoints include changes in HbA1c and fasting plasma glucose (FPG). The safety of vildagliptin in renal transplant patients will be assessed by the number of symptomatic hypoglycemic episodes (glucose Discussion NODAT is a severe complication after kidney transplantation. Few trials have assessed the safety and efficacy of antidiabetic drugs for these patients. The purpose of this study is to assess the safety and efficacy of vildagliptin in renal transplant patients with NODAT. Trial Registration ClinicalTrials.gov NCT00980356