leukotriene-b4 and Vascular-Diseases

This double-blind study was designed to examine and compare the effects of supplementing the existing diet with fish oil or olive oil on lipids and cell function in patients with peripheral vascular disease. Thirty-two patients with symptomatic and angiographically demonstrated peripheral vascular disease were screened, matched, and randomly allocated to take either 15 g/d fish oil or olive oil for 4 weeks. Fish oil reduced serum triglyceride levels by 26%, but increased total cholesterol levels due to a significant increase in both low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein-2 cholesterol (HDL2-C). There was a nonsignificant decrease in HDL3-C levels. Olive oil reduced total cholesterol levels, accountable to a significantly decrease in LDL-C levels. Serum thromboxane B2 (TXB2) levels remained unchanged following fish oil, but were significantly increased by olive oil. Urinary excretion of TXB2 and 6-keto-PGF1 alpha was unaffected by either oil supplement. Platelet aggregation, which was measured in platelet-rich plasma in response to two doses of collagen or platelet-activating factor (PAF), was significantly reduced after fish oil, but was increased by olive oil. Following fish oil, there was a significant increase in eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid (DHA, 22:6) levels and a decrease in arachidonic acid content of platelet phospholipids. The platelet fatty acid composition after olive oil was unchanged. Fish oil decreased neutrophil leukotriene B4 (LTB4) generation following calcium ionophore stimulation by 33%, while leukotriene B5 levels increased significantly. Neutrophil PAF production and plasma lyso-PAF were unaffected by either oil.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Aged; Blood Platelets; Cholesterol, HDL; Cholesterol, LDL; Dietary Fats, Unsaturated; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Fish Oils; Food, Fortified; Humans; Leukotriene B4; Lipids; Male; Middle Aged; Neutrophils; Olive Oil; Plant Oils; Thromboxane B2; Triglycerides; Vascular Diseases

Neutrophil activation with the release of intracellular granule contents has been observed in sickle cell disease (SCD). Because leukotriene B(4) (LTB(4)), a 5-lipoxygenase metabolite of arachidonic acid in neutrophils, is a chemoattractant and enhances neutrophil adhesion to endothelium, we assessed plasma levels of this metabolite in controls (n = 9) and individuals with SCD, SS genotype, both in basal "steady state" (n = 37) and during episodes of vaso-occlusion (n = 10) and acute chest syndrome (n = 5). Thirteen patients with SCD, SC genotype, in steady state were also studied. Although no significant differences were noted between the control (136 +/- 32 fmol/mL) and SC genotype (177 +/- 83 fmol/mL, P >.15), LTB(4) levels were markedly increased in patients with SS genotype in basal steady state (207 +/- 64 fmol/mL, P <.003) compared with those in controls. Values were further increased during vaso-occlusion (264 +/- 94 fmol/mL) and acute chest syndrome (363 +/- 124 fmol/mL). These levels were significantly different from measurements taken during steady state (P <.04 and P <.0001, respectively). No correlation was noted between LTB(4) level and total white cell or neutrophil count. Additionally, the significant correlation noted in SCD between increased levels of plasma LTB(4) and soluble L-selectin (P <.03) reflects neutrophil activation. We also observed an effect of LTB(4) on red cell-endothelial adhesion at concentrations that appear clinically relevant (1-10 pmol/mL) with concomitant up-regulation of mRNA for the endothelial vitronectin receptor. These properties of LTB(4) are relevant to disease pathophysiology, providing further evidence of the contribution of the neutrophil to the proinflammatory and proadhesive phenotype in SCD.

Topics: Adolescent; Adult; Anemia, Sickle Cell; Cell Adhesion; Chest Pain; Child; Child, Preschool; Endothelium, Vascular; Erythrocytes; Fetal Hemoglobin; Gene Expression; Genotype; Hemoglobins; Humans; L-Selectin; Leukocyte Count; Leukotriene B4; Neutrophils; Pain; Receptors, Vitronectin; Reference Values; Reticulocyte Count; RNA, Messenger; Syndrome; Vascular Diseases

The eicosanoids are a family of lipid-derived autocoids that are released in response to a variety of physical and hormonal stimuli. In this study, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) were measured in the digital veins of clinically normal horses and horses with chronic laminitis to determine whether these arachidonic acid metabolites have a role in mediating signs of hoof pain and lesions associated with chronic laminitis. Horses were evaluated at rest and after a brief exercise period, to determine whether eicosanoids are released into the circulation after mild concussion. Digital vein eicosanoid concentrations in horses with signs of hoof pain attributable to chronic laminitis were not different than those in clinically normal horses. There was no difference in resting and postexercise PGE2 or LTB4 concentrations. Mean digital vein PGE2 concentration for the 2 groups was 187.18 pg/ml, whereas mean digital vein LTB4 concentration for the 2 groups was 74.71 pg/ml. These data do not support the hypothesis that PGE2 and LTB4 have a role in mediating the signs of pain and pathologic features of chronic laminitis.

Topics: Analysis of Variance; Animals; Chronic Disease; Dinoprostone; Eicosanoids; Female; Foot; Horse Diseases; Horses; Leukotriene B4; Male; Orchiectomy; Reference Values; Syndrome; Vascular Diseases; Veins