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Responses of vascular endothelial oxidant metabolism to lipopolysaccharide and tumor necrosis factor-alpha.

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Quantification of intracellular and extracellular levels and production rates of reactive oxygen species is crucial to understanding their contribution to tissue pathophysiology. We measured basal rates of oxidant production and the activity of xanthine oxidase, proposed to be a key source of O2-

The 4-amino analogue of tetrahydrobiopterin efficiently prolongs murine cardiac-allograft survival.

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We tested the 4-amino analogue of tetrahydrobiopterin (H(4)aminobiopterin), a novel pterin-based inhibitor of nitric oxide synthases, for its efficacy in a murine cardiac-transplant model employing an improved cuff technique. We treated groups of 5 animals each for the first 7 post-operative days

Induction of guanosine triphosphate-cyclohydrolase by follicle-stimulating hormone enhances interleukin-1 beta-stimulated nitric oxide synthase activity in granulosa cells.

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In cultured granulosa cells, interleukin-1 beta (IL-1 beta) induced a time-dependent (16-72 h) and dose-related (0.3-30 ng/ml) stimulation of nitric oxide (NO) synthase (NOS) activity, as determined by the catalytic conversion of [3H]arginine to [3H]citrulline and NO2- accumulation in the culture

Role of tetrahydrobiopterin availability in the regulation of nitric-oxide synthase expression in human mesangial cells.

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Human mesangial cells express an inducible form of nitric-oxide synthase (iNOS) after treatment with cytokines. Tetrahydrobiopterin (BH4), an essential cofactor for NOS, is required for cytokine-induced NO generation. We report here that BH4 is necessary not only for the activity but also for the

Regulation of inducible nitric oxide production by cytokines in human thyrocytes in culture.

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We now report on the induction and modulation of NO production by cytokines in primary cultures of human thyrocytes and the effect of NO on iodine organification by human open thyroid follicles in the process of thyroid hormone biosynthesis. Although unstimulated thyrocytes produced little NO

Protection against endotoxemia in rats by a novel tetrahydrobiopterin analogue.

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We studied the effects of a novel pterin antagonist of NO synthase, the 4-amino analogue of tetrahydrobiopterin (4-ABH4), in a rat model of endotoxic shock and compared its properties with those of N(G)-monomethyl L-arginine (L-NMMA). Treatment with a bolus dose of 4-ABH4 at 2 h after LPS challenge

Tetrahydrobiopterin biosynthesis defects examined in cytokine-stimulated fibroblasts.

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Incubation of primary skin fibroblast cultures with the cytokines interferon-gamma and tumour necrosis factor-alpha stimulates the de novo pathway of tetrahydrobiopterin biosynthesis. Fibroblasts from patients with the two most common types of genetic defects of tetrahydrobiopterin metabolism that

Cerebral folate deficiency syndromes in childhood: clinical, analytical, and etiologic aspects.

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BACKGROUND Cerebral folate deficiency may be amenable to therapeutic supplementation. Diverse metabolic pathways and unrelated processes can lead to cerebrospinal fluid 5-methyltetrahydrofolate (5-MTHF) depletion, the hallmark of cerebral folate deficiency. OBJECTIVE To analyze cerebral folate

Neopterin formation and tryptophan degradation by a human myelomonocytic cell line (THP-1) upon cytokine treatment.

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Determination of neopterin [D-erythro-6-(1',2',3'-trihydroxypropyl)pterin] in body fluids is a powerful diagnostic tool in a variety of diseases in which activation of cellular immune mechanisms is involved, such as certain malignancies, allograft rejection, and autoimmune and infectious diseases.

Regulation of tetrahydrobiopterin synthesis and bioavailability in endothelial cells.

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Tetrahydrobiopterin (BH4) is a member of the pterin family that has a core structure of pyrazino-2,3-d-pyrimidine rings. Because BH4 is an essential cofactor for the biosynthesis of nitric oxide (a major vasodilator), there is growing interest in BH4 biochemistry in endothelial cells (the cells that

Cytokine-activated endothelial cells express an isotype of nitric oxide synthase which is tetrahydrobiopterin-dependent, calmodulin-independent and inhibited by arginine analogs with a rank-order of potency characteristic of activated macrophages.

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We have previously reported that cultured murine brain endothelial cells (MBE) produce large quantities of nitric oxide (NO) after activation with interferon-gamma in combination with any of several immunoactivators including: bacterial endotoxin, tumor necrosis factor and interleukin-1. Since

The role of xanthine oxidase and xanthine dehydrogenase in skin ischemia.

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The importance of sequential events which lead to skin necrosis has significant implications in trauma, vascular injury, and wound healing. In this series of experiments, we tested the hypothesis that xanthine oxidase (XO) activity was increased along an ischemic gradient of a skin flap and that the

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