Article

Influence of pegylated interferon-alpha therapy on plasma levels of citrulline and arginine in melanoma patients.

Department of Neuroscience, Erasmus MC, The Netherlands.
Amino Acids (Impact Factor: 3.65). 02/2007; 32(1):121-6. DOI: 10.1007/s00726-006-0284-3
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ABSTRACT The aim of this study was to evaluate the effect of pegylated interferon-alpha (PEG-IFN-alpha) on the plasma citrulline/arginine ratio, regarded as an index of nitric oxide (NO) synthesis, in patients with high-risk melanoma. Forty patients were randomly assigned to either PEG-IFN-alpha treatment (n = 22) or to observation only (control group, n = 18). The treatment group received 6 microg PEG-IFN-alpha/kg once a week during 8 weeks, followed by a maintenance dose of 3 microg/kg/wk. Blood was collected at different time points, plasma concentrations of citrulline and arginine were measured and the ratio of citrulline/arginine was calculated. Patients treated with PEG-IFN-alpha showed a significant decrease in the concentrations of citrulline and in the citrulline/arginine ratio during the whole study period, both compared to baseline values and to the control group. The data suggest that therapy with PEG-IFN-alpha results in a marked decrease in the synthesis of NO in melanoma patients.

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    • "On the one hand, one could doubt the validity of the use of the amino acids CIT and ARG as indices for NO production as the metabolism of CIT and ARG is complex. This has already been discussed earlier (Fekkes et al. 2007). On the other hand, the assay of NOx is fraught with technical difficulties and blood concentrations of nitrite/nitrate are influenced by factors as diet, physical activity and antioxidants taken (Tsikas and Frölich 2004; Dusse et al. 2005). "
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    Amino Acids 10/2009; 37(4):703-708. DOI:10.1007/s00726-008-0191-x · 3.65 Impact Factor
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    • "In this process tetrahydrobiopterin (BH4) is a necessary cofactor. We have shown that the ratio of the plasma concentrations of citrulline (Cit) and arginine (Arg), the so-called Cit/Arg ratio, can be regarded as an index of NO synthesis (Fekkes et al. 2007). One of the key players in the production of NO in AD may be the inflammation and immune activation that characterize the pathology of AD. "
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    Amino Acids 06/2009; 38(3):923-8. DOI:10.1007/s00726-009-0300-5 · 3.65 Impact Factor
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    ABSTRACT: There is an increasing interest in the role of nitric oxide (NO) and pterines in the pathophysiology of neuropsychiatric disorders. The results so far show an inconsistent pattern. In the present study, neopterin and a measure of NO synthesis in plasma of symptomatic and euthymic bipolar affective patients were compared to those of patients with a major depression and healthy controls. As an index of NO synthesis, the ratio of the amino acids citrulline and arginine (Cit-Arg ratio) was calculated. Neopterin is a bypass product in the synthesis of tetrahydrobiopterin, which is a cofactor of NO synthase. The results indicate that both neopterin and the Cit-Arg ratio are decreased in bipolar affective patients, irrespective of their symptomatic status. In addition, an association between the values of the Cit-Arg ratio and the neopterin level was observed, which is suggestive for a low tetrahydrobiopterin activity. NO formation may be endangered in bipolar affective disorder.
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