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Introduction The incidence of cardiovascular events increases at the onset of menopause. Failing ovarian function is associated with an increase in blood levels of C-reactive protein (CRP), fibrinogen, interferon-γ (Pfeilschifter [...], Raloxifene (RLX), a selective oestrogen receptor modulator, has oestrogen-agonisi effects on bone, lipoproteins, and homocysteine and oestrogen-antagonist activity in the breast and uterus, positioning it as a potential drug for long-term prevention of coronary heart disease in postmenopausal women. To further evaluate its influence on cardiovascular risk factors, we studied the effects of 60 mg/day RLX on serum lipid levels, inflammatory (high-sensitivity C-reactive protein, and coagulation (fibrinogen) markers, monocytes, and fibrinolysis in 15 healthy postmenopausal women. Markers were measured at baseline, after 1 month without treatment, and after 3 months of treatment. Fibrinolysis was evaluated using the euglobulin clot lysis time (ECLT) determined with a new semiautomatic optical method. Monocyte phenotype was determined by measurement of the expression of the antigens CD14, HLA-DR. and CD62-L using flow cytometry. After 3 months of RLX treatment, we observed a decrease in total cholesterol (p = 0.002), in low-density lipoprotein cholesterol (p Key words: monocytes, raloxifene, CDI4, CD62-L, phenotype. Le raloxifene (RLX), un modulateur selectif du recepteur des oestrogenes, reproduit les effets agonistes des oestrogenes sur l'os, les lipoproteines et l'homocysteine, et l'activite antagoniste des oestrogenes dans le sein et l'uterus, ce qui le positionne comme medicament potentiel de prevention de la coron aropathie a long terme chez les femmes postmenopausees. Pour evaluer son influence sur les facteurs de risques cardiovasculaires, nous avons examine les effets de 60 mg/jour de RLX sur les taux de lipides seriques, les marqueurs d'inflammation (proteine C-reactive a haute sensibilite) et de coagulation (fibrinogene), les monocytes et la fibrinolyse chez 15 femmes postmenopausees en sante. Nous avons mesure les marqueurs au debut, apres 1 mois sans traitement et apres 3 mois de traitement. Nous avons evalue la fibrinolyse en utilisant le temps de lyse des euglobulines (TLE). determine par une nouvelle methode optique se mi automatique. Nous avons determine le phenotype des monocytes en mesurant l'expression des antigenes CD14, HDLA-DR et CD62-L au moyen de la methode de cytometric en flux. Apres 3 mois de traitement au RLX, nous avons observe une diminution du taux de cholesterol total (p = 0,002), des lipoproteines de faible densite cholesterol (p < 0.001) et des lipoproteins A (p = 0,01). Le taux de fibrinogene (p = 0,002) a diminue de maniere significative et celui de la proteine C-reactive a haute sensibilite a eu tendance a diminuer, mais cette diminution n'a pas atteint une signification statistique (p = 0,006). Le traitement au RLX n'a pas eu d'effet sur le TLC (p = 0,223) ni sur les numerations leucocytaires, lymphocytaires ou monocytaires totales (p = 0.313). Le traitement n'a pas modifie l'expression monocytaire de HLA-DR, CDI4 et CD62-L. Ainsi, nous confirmons que le RLX a des effets benefiques a court terme sur les taux des lipids et des marqueurs de l'inflammation, et qu'il n'a aucun effet sur la fibrinolyse ou le phenotype monocytaire. Mots-cles: monocyte, raloxifene, CD14, CD62-L, phenotype. [Traduit par la Redaction]

The oxidation theory proposes that LDL oxidation is an early event in atherosclerosis and that oxidized LDL contributes to atherogenesis in triggering inflammation. In contrast to the copper-modified LDL, there [...]

Abstract Background Endothelial cell dysfunction, by promoting fibrin deposition, has been implicated in the development of multiple organ failure. Altered fibrinolysis during inflammation may participate in microvascular alterations. We sought to determine whether plasma fibrinolysis was related to the severity of organ dysfunction and/or to the levels of von Willebrand factor (vWF antigen), as a marker of endothelium dysfunction, in critically ill patients. Methods Forty-nine consecutive patients admitted to an adult medico-surgical intensive care unit (ICU) with (18) or without sepsis (31) were included. C-reactive protein and vWF levels were measured on ICU admission and plasma fibrinolysis was assessed by the Euglobulin Clot Lysis Time (ECLT). The sequential organ failure assessment (SOFA) score and the simplified acute physiology score (SAPS) II were calculated on admission. Results ECLT was significantly longer in septic than in non-septic patients [1033 min (871–1372) versus 665 min (551–862), p = 0.001]. There were significant correlations between ECLT and C-reactive protein (CRP) concentrations (r = 0.78, p < 0.001) and the Sequential Organ Failure Assessment (SOFA) score (r = 0.39, p = 0.006). The level of vWF was not correlated with the ECLT (r = -0.06, p = 0.65) or the SOFA score (r = -0.02, p = 0.88). Conclusion ECLT measurement at admission could be a marker of organ dysfunction and a prognostic indicator in critically ill patients.

Background: Blood fluidity is maintained by a delicate balance between coagulation and fibrinolysis. The endothelial cell surface is a key player in this equilibrium and cell surface disruptions can upset the balance. We investigated the role of pericellular myeloperoxidase oxidized LDLs (Mox-LDLs) in this balance. Methods and Results: We designed a technical device that enabled us to monitor fibrinolysis in real-time at the surface of an endothelial cell line (EA.hy926), and showed that Mox-LDL decreased pericellular fibrinolysis. There were no changes in fibrinolysis when EA.hy926 endothelial cells were exposed to native LDL (24 hours) at doses of 10, 50, 100 and up to 1250 μg/ml. However, treatment of EA.hy926 endothelial cells with 10 and 50 mg/ml of Mox-LDL (physiological serum concentrations) increased the lysis time by 15 and 13%, respectively (p<0.001), although this effect was not present at higher concentrations of 100 mg/ml. This effect was not correlated with any changes in PAI-1 or t-PA or PA Receptor (PAR) expression. No effect was observed at the surface of smooth muscle cells used as controls. Conclusion: Our data link the current favorite hypothesis that modified LDL has a causal role in atheroma plaque formation with an old suggestion that fibrin may also play a causal role. Our data help complete the paradigm of atherosclerosis: Modified LDL locally enhances fibrin deposition (present work); fibrin deposits enhance endothelial permeability; this effect allows subendothelial accumulation of lipid and foam cells. [ABSTRACT FROM AUTHOR]

Several letters to the editor are presented in response to the articles "Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus" in the 2012 issue of the periodical and a response by the authors to these letters are also included.

Presents several correspondence concerning global scientific issues as of August 1982. Decay mode for protons; Accuracy of the lie detectors; Effectiveness of Maalox in treating ulcers.