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Cells in target organs such as liver do not generally incorporate tetrahydrobiopterin (BH4) in its fully reduced form. Instead, they transiently take up BH4 from the extracellular fluid, instantaneously oxidize it and then expel virtually all of it. However, a small but stable accumulation of BH4 was observed after BH4 administration to the cell cultures.(More)
OBJECTIVE Endothelial nitric oxide synthase (eNOS) activity is supported by tetrahydrobiopterin (BH4), which appears to be important for generating protective NO but decreases uncoupling formation of superoxide. We investigated the effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, in terms of BH4 metabolism in human(More)
OBJECTIVE Although it has been reported that oral administration of tetrahydrobiopterin (BH4) prevents endothelial dysfunction and vascular oxidative stress in various rat models, the effect of treatment with BH4 on atherogenesis remains unclear. METHODS AND RESULTS In this study, we investigated whether oral BH4 treatment might slow the progression of(More)
Porcine edema disease (ED) is caused by Shiga toxin 2e-producing Escherichia coli (STEC). ED has become frequent in pig farms, and the use of antimicrobials has resulted in the development of antimicrobial-resistant STEC. Accordingly, the use of materials other than antimicrobials is requested for the prevention of ED. Oral administration of a heat-killed(More)
OBJECTIVE The pteridine cofactor tetrahydrobiopterin (BH4) has emerged as a critical determinant of endothelial nitric oxide synthase (eNOS) activity. When BH4 availability is limited, eNOS does not produce nitric oxide (NO) but instead generates superoxide. BH4 may reverse endothelial dysfunction due to cardiovascular disease, including atherosclerosis,(More)
Diarrhea in pigs has the potential to have a serious economic impact on the swine industry. Previously, we suggested that the likely cause of the presence of non-infectious diarrhea in pigs characterized by lactate accumulation was dyspepsia. In this experiment, the prevalence of enteropathogens and hyper-lactate accumulation in feces of piglets in 4(More)
The authors evaluated whether supplementation of tetrahydrobiopterin (BH4) or the BH4 precursor in vascular smooth muscle cells (VSMC) that are deficient in de novo BH4 production affected the ability of these cells to synthesize nitric oxide (NO). GTP cyclohydrolase I (GTPCH) is the rate-limiting enzyme for the de novo synthetic pathway of BH4. The(More)
OBJECTIVE We investigated the effects of the statins, cerivastatin and fluvastatin, on the induction of nitric oxide (NO) production in vascular smooth muscle cells (VSMC) stimulated by interleukin-1beta (IL-1) or in combination with interferon-gamma (IFN). METHODS We measured NO release, inducible NO synthase (iNOS) mRNA and protein levels, iNOS gene(More)
Porcine edema disease (ED) is caused by Shiga toxin 2e-producing Escherichia coli (STEC). Post-weaned piglets often suffer from ED as a result of intestinal infection with STEC, which causes impaired growth performance and high mortality. Antimicrobial therapy is a curative treatment for piglets infected with STEC, but the emergence of(More)