Urinary leukotriene E4 excretion: a biomarker of inflammatory bowel disease activity.

Background: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders collectively referred to as inflammatory bowel diseases (IBD). Cysteinyl leukotrienes are proinflammatory 5-lipoxygenase-derived products that play a major role in the immune and inflammatory response. Consequently, they may be involved in the pathogenesis of IBD.

[Immunosuppressive drugs and highly active antiretroviral therapy: pharmacokinetic interactions].

The development of highly active antiretroviral therapy has greatly improved HIV-infected patient survival. However, the increased life expectancy associated with the management of opportunistic infections might favour the onset of severe organic failure that could require organ transplantation. The use of immunosuppressive drugs in association with antiretroviral therapy will generate pharmacodynamic and pharmacokinetic interactions.

Effect of 5-lipoxygenase blockade on blood pressure and acetylcholine-evoked endothelium-dependent contraction in aorta from spontaneously hypertensive rats.

Objective: Cysteinyl leukotrienes (cysLT) are pro-inflammatory and vasoactive products suspected to be involved in the regulation of vascular tone and blood pressure in hypertension.

Design: We investigated, in spontaneously hypertensive rats (SHR), the involvement of cysLT in the in-vivo regulation of blood pressure and the in-vitro endothelium-dependent contraction to acetylcholine in isolated aorta.

Methods: SHR and Wistar-Kyoto rats (WKY) were orally treated for 3 weeks with either the cysLT biosynthesis inhibitor MK-886 (0.

Urinary leukotriene E4 excretion is increased in type 1 diabetic patients: a quantification by liquid chromatography-tandem mass spectrometry.

Objective: Diabetes mellitus is associated with inflammatory state and increased cardiovascular mortality. Leukotrienes are arachidonic acid metabolites derived from the 5-lipoxygenase pathway that possess vasoactive, chemotactic and proinflammatory properties. The aim of this study was to evaluate (1) the urinary excretion of leukotriene E4 (LTE4) in type 1 diabetic subjects and healthy volunteers and (2) the influence of glycemic control attested by HbA(1C) on LTE4 excretion.

Vascular effects of 15-F2t-isoprostane in spontaneously hypertensive rats.

F2-isoprostanes are a family of compounds derived from arachidonic acid by free radical-catalyzed peroxidation. Among F2-isoprostanes, 15-F2t-IsoP is a vasoconstrictor in animal and human vascular beds. Several recent studies found increased 15-F2t-IsoP levels in animal models of hypertension.

Functional assessment of vascular reactivity after chronic intermittent hypoxia in the rat.

We recently developed a model of chronic intermittent hypoxia (CIH) (FiO2 5%, 8 h/day, 35 days) in the rat that was associated with an increased infarction in isolated heart. The aim of the present study was to characterize its functional consequences on vasoreactivity. Aorta and carotid artery were studied using organ bath technique while mesenteric vascular bed was perfused.

15-F-isoprostane and 5-F-isoprostane are not triggers of myocardial preconditioning.

1. Myocardial ischaemia-reperfusion in humans is associated with increased formation of 15-F(2t)-isoprostane and 5-F(2t)-isoprostane (15-F(2t)-IsoP and 5-F(2t)-IsoP, respectively). Whether this formation is relevant clinically remains controversial.

Effects of short-term treatment with vitamin E in systemic sclerosis: a double blind, randomized, controlled clinical trial of efficacy based on urinary isoprostane measurement.

This double blind randomized controlled trial was designed to investigate whether short-term vitamin E treatment at doses of 500 and 1000 mg/day, compared to placebo, decreased urinary F(2)-isoprostanes and improved the microvascular perfusion after cold exposure in patients suffering from SSc. Thirty-three eligible patients were randomly assigned in a 1.3:1:1 ratio to receive placebo, vitamin E 500 mg, or vitamin E 1000 mg daily for 3 weeks.

[Genetic polymorphism and treatment of chronic bowel inflammatory diseases: the example of azathioprine].

Azathioprine is an immunosuppressive drug used in the treatment of inflammatory bowel disease. It is a prodrug that is hydrolysed to 6-mercaptopurine, which represents the active form. Azathioprine is also used in the treatment of leukaemia in children and in organ transplantation.

2-Arachidonoyl glycerol induces contraction of isolated rat aorta: role of cyclooxygenase-derived products.

Objectives: Endocannabinoids have been shown to play a role in the regulation of vascular tone. The effects of 2-arachidonoyl glycerol (2-AG) on induced-tone were examined in rat aortic rings in vitro.

Methods: Aortic rings from Wistar Kyoto (WKY) rats were suspended in organ chambers for recording isometric tension development in response to 2-AG.

Inhibition of leukotriene synthesis with MK-886 prevents a rise in blood pressure and reduces noradrenaline-evoked contraction in L-NAME-treated rats.

(1) Long-term treatment of rats with Nomega-nitro-l-arginine methyl ester (l-NAME) induces hypertension associated with inflammatory and vascular changes. Leukotrienes are proinflammatory vasoactive products that are suspected to be involved in the pathogenesis of hypertension. We investigated, in rats chronically treated with l-NAME, the involvement of leukotrienes in the in vivo regulation of blood pressure and the in vitro contraction elicited by noradrenaline in isolated aorta.

Functional comparison of the antagonistic properties of some Angiotensin II type 1 receptor blockers on the contraction elicited by Angiotensin II and thromboxane A2 on human saphenous veins.

We previously described on human vascular preparations that, in addition to its antagonistic properties on Angiotensin II type 1 (AT1) receptor, losartan could also inhibit the contraction elicited by the stable thromboxane A2 mimetic U46619. The present study was designed (1) to investigate, in human vascular preparations (the saphenous veins) whether these antagonistic properties on thromboxane A2/prostaglandin H2 (TP) receptor were shared by some other AT1 receptor antagonists (irbesartan and valsartan) and the active metabolite of losartan EXP3174, and (2) to compare their antagonistic properties on TP receptors to their antagonistic properties on AT1 receptors. In the presence of indomethacin (10 microM) and Nomega-nitro-L-arginine (100 microM), irbesartan, valsartan, and EXP3174 induced a rightward shift of U46619- and angiotensin II-induced contraction.

Lipid peroxidation is not increased in patients with untreated mild-to-moderate hypertension.

In contrast with the huge amount of experimental data available, only few and somewhat unconvincing clinical studies support the hypothesis that oxidative stress is involved in the early stages of essential hypertension in humans. Isoprostanes are chemically stable lipid peroxidation products of arachidonic acid, the quantification of which provides a novel approach to the assessment of oxidative stress in vivo. The main objective of this study was to quantify the urinary levels of 15-F(2t)-IsoP in the early stages of essential hypertension, using gas chromatography/mass spectrometry, by comparing 30 patients with never-treated mild-to-moderate hypertension with 30 gender- and age-paired healthy controls.

Ribavirin quantification in combination treatment of chronic hepatitis C.

Ribavirin in combination with alpha 2 interferon is the consensus treatment for chronic hepatitis C. However, recent preliminary pharmacological studies have suggested that the bioavailability of ribavirin displays great interindividual variability. In order to monitor serum ribavirin levels during combination treatment, we developed and validated a quantitative assay using an approach adaptable for routine hospital laboratories.

Isoprostanes as a biomarker of lipid peroxidation in humans: physiology, pharmacology and clinical implications.

Isoprostanes are a complex family of compounds produced from arachidonic acid via a free-radical-catalyzed mechanism. They can be quantified as reliable markers of lipid peroxidation. Among the isoprostanes, 15-F(2t)-IsoP and 15-E(2t)-IsoP are biologically active and mediate vasoconstriction and bronchoconstriction and augment nociception.

Effects of modafinil on heat thermoregulatory responses in humans at rest.

The effects of modafinil on heat thermoregulatory responses were studied in 10 male subjects submitted to a sweating test after taking 200 mg of modafinil or placebo. Sweating tests were performed in a hot climatic chamber (45 degrees C, relative humidity <15%, wind speed = 0.8 m x s(-1), duration 1.

Increased urinary F2-isoprostanes in systemic sclerosis, but not in primary Raynaud's phenomenon: effect of cold exposure.

Objective: F2-isoprostanes are free radical-dependent arachidonic acid metabolites that are used as clinical markers of lipid peroxidation in systemic sclerosis (SSc) and other microvascular diseases. The objectives of this study were to determine whether the basal urinary levels of F2-isoprostane in SSc patients differ from those in patients with primary Raynaud's phenomenon (RP) and to investigate whether F2-isoprostane formation correlates with the cutaneous microvascular perfusion decrease following cold exposure in SSc patients, patients with primary RP, and healthy controls.

Methods: Eleven women with RP secondary to SSc, 11 women with primary RP, and 11 healthy women were exposed to decreasing room temperature, from 25 degrees C to 15 degrees C, for 40 minutes.

The 5-series F(2)-isoprostanes possess no vasomotor effects in the rat thoracic aorta, the human internal mammary artery and the human saphenous vein.

1. Among the F(2)-isoprostanes, the 15- and the 5-series are currently used as markers of lipid peroxidation in vascular diseases. 15-F(2t)-IsoP (also named iPF(2 alpha)-III) exerts a vasoconstriction in most vessels, whereas no data is available concerning 5-F(2t)-IsoP (also named iPF(2 alpha)-VI), which is more abundant in plasma.

Response of rat thoracic aorta to F(2)-isoprostane metabolites.

This study was undertaken to investigate the vascular actions (contraction and relaxation) of the F(2)-isoprostane metabolites 15-keto-15-F(2t)-IsoP, 2,3-dinor-15-F(2t)-IsoP, and 2,3-dinor-5,6-dihydro -15-F(2t)-IsoP in comparison with 15-F(2t)-IsoP on the rat thoracic aorta. 15-keto-15-F(2t)-IsoP induced a vasoconstriction in a concentration-dependent manner with a pD(2) value of 5.80 +/- 0.

Involvement of cysteinyl leukotrienes in angiotensin II-induced contraction in isolated aortas from transgenic (mRen-2)27 rats.

Objectives: We have previously reported that 5-lipoxygenase-derived products, and particularly the cysteinyl leukotrienes (CysLTs), were involved in angiotensin II (Ang II)-induced contractions in isolated aortas from spontaneously hypertensive rats.

Design: The aim of this study was to assess the role of CysLTs in the vascular response to Ang II in an Ang II-dependent model of hypertension, the (mRen-2)27 transgenic rats (TGs).

Methods: Intact aortic rings from TG and normotensive Sprague-Dawley rats (SDs) were suspended in organ chambers for isometric tension development in response to Ang II.