Gender differences in copper, zinc and selenium status in diabetic-free metabolic syndrome European population - the IMMIDIET study.

BACKGROUND AND AIMS: The European 'IMMIDIET' study was designed to evaluate the effect of genetic and dietary habit interactions on cardiovascular disease risk factors in non-diabetic subjects. Copper, zinc and selenium are involved in redox balance and modifications of their homeostasis could be associated with metabolic syndrome. Because few studies have dealt with trace element status in metabolic syndrome with conflicting results, we aimed at investigating the relationships between plasma copper, zinc and selenium concentrations and metabolic syndrome in the IMMIDIET population. METHODS AND RESULTS: Male-female couples born and living in Abruzzo, Italy (n = 271); Limburg, Belgium (n = 267), southwest part of London, England (n = 263) and 205 Italian-Belgian mixed couples living in Belgium were enrolled. Data on medical history, hypertension and blood lipid profile, medication use, smoking and alcohol habits, physical activity and socioeconomic status were collected using a standardised questionnaire. Anthropometric, blood pressure, glucose, insulin, lipid profile and copper, zinc and selenium measurements were performed. Participants were classified in two groups according to the presence of metabolic syndrome (Yes/No). Comparison between these two groups, performed separately in men and women, indicated no association in men whereas, in women, metabolic syndrome was associated with higher plasma selenium concentrations (odds ratio (OR) = 1.55(1.28-1.89)); this association remained significant after adjustment for age, group, social status, physical activity, energy intake, alcohol consumption, smoking and hormonal status (OR = 1.33 (1.06-1.67)). CONCLUSION: Our results indicate gender differences in the association between plasma selenium concentration and metabolic syndrome without diabetes and may suggest a sub-clinical deleterious effect of high selenium status in women.

A new animal model of thrombophilia confirms that high plasma factor VIII levels are thrombogenic.

The thrombotic risk associated with elevated plasma levels of clotting factor VIII (FVIII) was investigated in a mouse model of thrombophilia. After the intravenous injection of recombinant human FVIII and/or of purified FVIII-free human von Willebrand factor (vWF), a controlled mild injury was inflicted on the carotid artery of FVB mice by irradiation with filtered green light in combination with intravenous injection of the dye rose bengal. Formation of a platelet-rich thrombus was continuously monitored for 40 min via transillumination and the thrombus size was measured via image analysis. Administration of recombinant human FVIII at 40 microg/kg led to initial FVIII plasma activities equivalent to 250% of normal human plasma FVIII activity and significantly enhanced thrombus size. Immunohistochemical staining illustrated the accumulation of FVIII within the thrombi. Human vWF, even at 10 mg/kg, had no effect on thrombus formation. The thrombotic tendency induced by FVIII was significantly inhibited by the administration of human vWF in a dose-dependent manner. Separate plasma measurements revealed that human FVIII has comparable affinities for human and murine vWF but that human vWF does not effectively bind murine platelets. The inhibition by human vWF of the thrombotic tendency induced by human FVIII could therefore be explained by a lack of accumulation of FVIII within the developing thrombus because of the reduced affinity of human vWF for murine platelets and the reduced occupancy of murine von Willebrand factor by human FVIII after injection of human vWF. These results show that vWF actively participates in FVIII accumulation in the arterial thrombus and provide experimental evidence for epidemiological findings that elevated plasma FVIII levels are associated with an increased thrombotic risk, also in arteries.

Comparison of a synthetic antithrombin III-binding pentasaccharide and standard heparin as an adjunct to coronary thrombolysis.

The effects on alteplase-induced thrombolysis of the synthetic ATIII-binding pentasaccharide SR90107A/ORG 31540 (synthetic pentasaccharide, SP) and of standard heparin (SH) were compared in a copper coil model of coronary artery thrombosis in 6 groups of 10 dogs. After 1 h of occlusion, all animals received intravenously alteplase and aspirin, and were randomly assigned to a 2 h infusion of either saline, or one of two doses of SH (100 IU/kg bolus plus 50 IU/kg/h infusion, or 200 IU/kg bolus plus 100 IU/kg/h infusion), or one of three doses of SP (100 nmol/kg bolus plus 50 nmol/kg/h infusion, 200 nmol/kg bolus plus 100 nmol/kg/h infusion, or 400 nmol/kg bolus plus 200 nmol/kg/h infusion). Coronary angiography was performed every 10 min for 4 h. Appropriate doses of SP and SH enhanced alteplase-induced thrombolysis to a similar extent. In contrast, SP was devoid of any anti-IIa activity or aPTT prolongation.

High-dose intravenous immunoglobulin treatment of a pregnant patient with an antiphospholipid syndrome: immunological changes associated with a successful outcome.

A patient with a history of habitual abortion, deep venous thrombosis, thrombocytopenia, high titer IgG anticardiolipin antibodies and a clearly positive lupus anticoagulant, was treated during her seventh pregnancy with high-dose intravenous immunoglobulins (IVIg) from the third month onwards. Every month, a daily infusion of 400 mg immunoglobulins per kg body weight was given during five consecutive days. The patient's pregnancy ended preterm with a live birth, delivered by caesarian section because of a placental abruption. The 1070 g (P20-P25) weighing girl was in good health, apart from a bradycardia, due to dysfunction of the atrioventricular conduction. Each treatment with IVIg resulted in a slight reduction of both anticardiolipin antibodies and lupus anticoagulant levels and in an increase in platelet count. During the six-month observation period, a gradual decline in antiphospholipid antibodies and an increase in platelet count was found. The potential role of anti-idiotypic antibodies, present in the IVIg used for treatment, was studied. In vitro, IVIg were able to reduce the binding of the patient's anticardiolipin antibodies to cardiolipin coated microtiter plates. The presence of anti-idiotypic antibodies in IVIg was further documented by affinity chromatography and by realtime biospecific interaction analysis (BIA) on a BIA-core instrument. Affinity purified anticardiolipin antibodies were retarded on a column of insolubilized IVIg and a weak interaction was found between IVIg and affinity purified antiphospholipid antibodies, coupled to the BIA-core biosensor. In addition, the same technology revealed increased levels of anti-antiphospholipid antibodies in the patient's plasma following IVIg therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Autotransfusion during aorto-iliac surgery.

Red blood cell (RBC) quality and function during autotransfusion with the Solcotrans system were studied. Up to 64% (mean 999.5 +/- 310 ml) of the total volume of blood lost (mean 1895 +/- 707 ml) during operation in 10 patients undergoing elective abdominal aortic surgery was salvaged. No patient received homologous blood during surgery. Haemoglobin (Hb) and Haematocrit (PCV) values decreased but within acceptable limits. No evidence of DIC was found and renal function was unaffected. Mechanical and functional damage to the RBC was minimal and erythrocyte oxygen-carrying capacity was excellent. 2,3-DPGRBC concentration and RBC reduced glutathion were normal. The device was easy to handle and technical problems were not encountered. It was accurate in salvaging blood although the need for homologous blood was not entirely eliminated since four patients received homologous blood products in the postoperative period. No adverse clinical events occurred.