M Sanchez Crespo

Varicose Veins Show Enhanced Chemokine Expression

OBJECTIVES Leucocyte infiltration in the wall of varicose veins has been reported previously. This study was designed to investigate the expression of pro-inflammatory cytokines and chemokines in control and in patients with varicose veins and to test the effect of treating varicose vein patients with acetylsalicylic acid (ASA) on cytokine expression prior to removal of varices. MATERIAL AND METHODS Sections of vein were removed during operation from both patient groups, and ribonuclease protection assays (RPAs) were performed to assess the expression of chemokines. Group I included non-varicose saphenous veins from healthy patients undergoing amputation for trauma. Varicose veins were obtained from patients with primary varicose undergoing surgical treatment who received no drug (group II) or treatment with 300 mg day(-1) of ASA for 15 days before surgery (group III). RESULTS Non-varicose veins constitutively expressed low levels of monocyte-chemoattractant protein (MCP-1) and interleukin (IL)-8 mRNA. Varicose veins had a distinct chemokine expression pattern, since significant up-regulation of MCP-1 and IL-8 and a marked expression of IP-10, RANTES, MIP-1alpha and MIP-1beta mRNA were detected. Removal of the endothelium did not alter this pattern. Varicose veins obtained from patients treated with ASA showed a consistent decrease in chemokine expression, although it did not reach statistical significance. CONCLUSIONS Varicose veins showed increased expression of several chemokines compared to control veins. A non-significant reduction of activation was observed following treatment with ASA for 15 days.

Non-platelet-mediated vascular actions of 1-O-alkyl-2-acetyl-sn-3-glyceryl phosphorycholine (a synthetic PAF)

Rat platelets fully responsive to thrombin and collagen did not release3H-serotonin with up to 10 μg/ml synthetic PAF. Therefore, an experimental approach using57Co and113Sn radiolabelled microspheres was developed to evaluate the effect of PAF on cardiac output (CO), peripheral vascular resistance (PVR) and redistribution of CO among organs. The effect on vascular permeability was studied by measuring the clearance of125I-HSA and the variations of the haematocrit. A significant fall in blood pressure and PVR was found with doses of PAF from 50 to 5000 ng. Moreover, the highest doses of PAF induced also a marked reduction in blood volume. A significant fall in spleen, coronary and kidney output was found but not in CO. Our data show that PAF, by itself, induces a fall in PVR and at higher doses also in circulating volume, both accounting for the hypotensive effect. The redistribution of CO seems to be the expression of a non-uniform action upon PVR.

Modulation of PAF biosynthesis in human polymorphonuclear leukocytes. The role of phorbol esters and protein kinases.

The biosynthesis of PAF (1-0-hexadecyl/octadecyl2-acetyl-sn-glycero-3-phosphocholine) in human polymorphonuclear leukocytes (PMN) has been extensively studied in recent years. This has allowed the delineation of two important features of this process that are widely accepted. First, the generation of PAF only occurs after the activation of the cell by secretagogues in the presence of extracellular calcium, and, second, this generation may be modulated by interfering with the process of cell activation. A number of studies have emphasized the role of the enzyme 1-0-hexadecyl2lysos n glycero3phosphocholine: acetyl-CoA acetyltransferase (EC 2.3.1.67) as the limiting step in the biosynthesis of PAF [1-4]. A logical consequence of the above-mentioned concept should be the correlation of the events which occur during cell activation with the stimulation of both acetyltransferase activity and PAF biosynthesis. This has been carried out in preparations other than PMN by studying the role of calcium ions and a phosphorylation-dephosphorylation mechanism in rat macrophages and spleen microsomes [5, 6]. PAF can also be synthesized from alkyl-acetyl-snglycerol and CDP-choline through DTT-insensitive cholinephosphotransferase (EC 2.7.8.16), but no evidence has been as yet provided as to the involvement of this pathway in PAF biosynthesis in PMN. Results and discussion

Immunoglobulin E-mediated anaphylaxis activates nuclear factor κB in rat small intestine

Abstract.Objective and Design: Since IgE-dependent reactions induce the inducible isoform of NO synthase, we postulated the involvement of the transcription factor NF-κB.¶Materials: 72 Wistar rats were divided into 6 groups and used to study the hemorrhagic necrosis of the small intestine elicited by anaphylaxis.¶Treatment: Passive anaphylaxis was produced by i.p. sensitization with IgE anti-dinitrophenyl monoclonal antibody and i.v. challenge with the cognate antigen.¶Methods: Competitive PCR was used to assay the expression of p50 subunit of NF-κB. κB-binding activity was assayed by electrophoretic mobility shift assay.¶Results: The PCR assay showed a time-dependent increase of mRNA coding for the p50 subunit of NF-κB, which was maximal 1 h after challenge (40 ± 3, versus 230 ± 32 f M, mean ± SEM) and decreased to prechallenge level at 4 h. κB-binding activity was also increased.¶Conclusions: IgE-mediated reactions trigger a pathway for nuclear signaling that seems to be related to the intermediate/late response of the allergic reaction.