95 research outputs found
In vivo effect of two first-line ART regimens on inflammatory mediators in male HIV patients
Emerging Roles of PAR-1 and PAFR in Melanoma Metastasis
Melanoma growth, angiogenesis and metastatic progression are strongly promoted by the inflammatory tumor microenvironment due to high levels of cytokine and chemokine secretion by the recruited inflammatory and stromal cells. In addition, platelets and molecular components of procoagulant pathways have been recently emerging as critical players of tumor growth and metastasis. In particular, thrombin, through the activity of its receptor protease-activated receptor-1 (PAR-1), regulates tumor cell adhesion to platelets and endothelial cells, stimulates tumor angiogenesis, and promotes tumor growth and metastasis. Notably, in many tumor types including melanoma, PAR-1 expression directly correlates with their metastatic phenotype and is directly responsible for the expression of interleukin-8, matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor, platelet-derived growth factor, and integrins. Another proinflammatory receptor–ligand pair, platelet-activating factor (PAF) and its receptor (PAFR), have been shown to act as important modulators of tumor cell adhesion to endothelial cells, angiogenesis, tumor growth and metastasis. PAF is a bioactive lipid produced by a variety of cells from membrane glycerophospholipids in the same reaction that releases arachidonic acid, and can be secreted by platelets, inflammatory cells, keratinocytes and endothelial cells. We have demonstrated that in metastatic melanoma cells, PAF stimulates the phosphorylation of cyclic adenosine monophosphate response element-binding protein (CREB) and activating transcription factor 1 (ATF-1), which results in overexpression of MMP-2 and membrane type 1-MMP (membrane type 1-MMP). Since only metastatic melanoma cells overexpress CREB/ATF-1, we propose that metastatic melanoma cells are better equipped than their non-metastatic counterparts to respond to PAF within the tumor microenvironment. The evidence supporting the hypothesis that the two G-protein coupled receptors, PAR-1 and PAFR, contribute to the acquisition of the metastatic phenotype of melanoma is presented and discussed
Impact of inactivity and exercise on the vasculature in humans
The effects of inactivity and exercise training on established and novel cardiovascular risk factors are relatively modest and do not account for the impact of inactivity and exercise on vascular risk. We examine evidence that inactivity and exercise have direct effects on both vasculature function and structure in humans. Physical deconditioning is associated with enhanced vasoconstrictor tone and has profound and rapid effects on arterial remodelling in both large and smaller arteries. Evidence for an effect of deconditioning on vasodilator function is less consistent. Studies of the impact of exercise training suggest that both functional and structural remodelling adaptations occur and that the magnitude and time-course of these changes depends upon training duration and intensity and the vessel beds involved. Inactivity and exercise have direct “vascular deconditioning and conditioning” effects which likely modify cardiovascular risk
Combined use of probucol and cilostazol with atorvastatin attenuates atherosclerosis in moderately hypercholesterolemic rabbits
SILICIC-ACID COLUMN CHROMATOGRAPHY OF PHOSPHONOLIPIDS .7. SEPARATION OF "1-O-ACETYL-3-O-GLYCERYLPHOSPHONATE, "1-O-OLEYL-2,3-GLYCERYLBIPHOSPHONATE AND "1,2-DIOLEYL-3-O-GLYCERYLPHOSPHONATE FROM THEIR PHOSPHORYL ANALOGS AND OTHER LIPIDS AND PHOSPHOLIPIDS
The biological activity of acetylated sphingosylphosphorylcholine derivatives
Taking into account their stereochemical similarity with
1-O-alkyl-2-acetyl-sn-glycerol-3-phosphorylcholine (PAF), which is known
to exhibit a diverse spectrum of biological actions, including platelet
aggregating and glycogenolytic activity, the acetylated derivatives of
sphingosylphosphorylcholine and sphingomyelin were synthesized and
tested for their ability to promote washed rabbit platelet aggregation
and glycogenolysis in Tetrahymena pyriformis cells. Sphingomyelin (SPM)
and sphingosylphosphorylcholine (SPC) were subjected to acetylation,
following chromatographic purification and physicochemical
characterization. The synthesized compounds N-acetyl, O-acetyl SPC (NAc,
OAc SPC), N-acetyl SPC (NAc SPC) and O-acetyl SPM (OAc, SPM) were tested
far their biological activity in the washed rabbit platelets and washed
Tetrahymena pyriformis cell systems. These derivatives induced [H-3]
serotonin and ATP release and a monophasic aggregation of washed rabbit
platelets in the concentration range 10(-8)-10(-6) M, However, authentic
PAF-induced washed rabbit platelet aggregation was inhibited at higher
concentrations of the acetylated sphingophospholipid compounds (> 10(-6)
M) and by the PAF-specific receptor(s) antagonists kadsurenone and
triazolam. Platelet desensitization and crossed desensitization
experiments with authentic PAF and the acetylated sphingophospholipids,
suggested interaction with the same receptor(s) as PAF and different
from the ADP or thrombin receptor. The involvement of calmodulin and
protein kinase C in the biological activity of the prepared analogues
was also demonstrated. Besides their action on rabbit platelets, the
PAF-like activity of the acetylated sphingophospholipids was also
demonstrated in a platelet-independent system, by showing that they
stimulate glycogenolysis in washed Tetrahymena pyriformis cells. These
observations indicate that a new class of compounds with PAF-like
activity were synthesized, but their role in the cellular metabolism
remains to be shown. The existence of acetylated sphingophospholipids
with PAF-like activity has so far been reported only in Urtica dioica
SEPARATION OF THE MAIN NEUTRAL LIPIDS INTO CLASSES AND SPECIES BY PR-HPLC AND UV DETECTION
A reversed phase high performance liquid chromatographic method is
described that allows separation and estimation of the main neutral
lipid classes as well as several species of each class. By the
represented method waxes, hydrocarbons, fatty acids and their methyl
esters, sterols and their esters, free glycerylethers, fatty alcohols,
vitamin E and mono-, di- and triglycerides are separated into classes
and into class species within 55min.
A stepped gradient elution with methanol/water, acetonitrile/methanol,
acetonitrile/tetrahydrofuran and isopropanol/acetonitrile was performed
onto a reverse phase C18 HPLC column and the effluent was monitored by W
detection at 206 nm.
Application of the method in a plant extract and in a vegetable oil
sample is represented
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