Microparticle-associated vascular adhesion molecule-1 and tissue factor follow a circadian rhythm in healthy human subjects

An increased risk of death or severe injury due to late-morning thrombotic events is well established. Tissue factor (TF) is the initiator of the coagulation cascade, and endothelial stresses, coupled with production of pro-coagulant microparticles (MP) are also important factors in loss of haemostasis. TF and vascular cell adhesion molecule-1 (VCAM-1) -positive cell microparticles were assessed periodically over a 24-hour (h) period in healthy human subjects to ascertain if they followed a circadian rhythm. Eleven healthy male subjects were assessed in a temperature-controlled environment with dietary intake consistent between subjects. Blood samples were taken every 4 h by venipuncture, and TF and VCAM-1 positive microparticles were quantified by flow cytometry. A significant circadian rhythm was observed in VCAM-1 MP (p=or<0.0001), and a trend was shown, although not statistically significant (p=0.065) in TF microparticles. A peak was observed at 9 a.m. for VCAM-1 positive MP, followed by a decrease and subsequent peak at 9 p.m. and a minimum at 5 a.m. TF-positive MP followed a strikingly similar trend in both variation and absolute numbers with a delay. A circadian rhythm was observed in VCAM-1 and less so TF-positive MP. This has significant implications in terms of the well known increased risk of cardiovascular thrombotic events matching this data. To our knowledge this is the first such report of quantified measurements of these MP over a 24-h period and the only measurement of a 24-h variation of in-vivo blood-borne TF

Pretreatment with hyperbaric oxygen and its effect on neuropsychometric dysfunction and systemic inflammatory response after cardiopulmonary bypass: a prospective randomized double-blind trial

Objective: Animal studies have shown that pretreatment with hyperbaric oxygen can induce central nervous system ischemic tolerance and also modulate the inflammatory response. We evaluated this therapy in patients undergoing cardiopulmonary bypass. Methods: Sixty-four patients were prospectively randomized to group A (n = 31; atmospheric air, 1.5 atmospheres absolute) or group B (n = 33; hyperbaric oxygen, 2.4 atmospheres absolute) before on-pump coronary artery bypass grafting. Age, sex, body mass index, diabetes, hypertension, smoking, coronary disease severity, left ventricular function, Parsonnet score, Euroscore, bypass time, myocardial ischemia time, and number of grafts were comparable in both groups. Canadian Cardiovascular Society angina, New York Heart Association dyspnea, and previous myocardial infarction were significantly higher in group B. Inflammatory markers were analyzed before surgery and 2 and 24 hours after bypass. Neuropsychometric testing was performed 48 hours before surgery and 4 months after surgery and included trail making A and B, the Rey auditory verbal learning test, grooved peg board, information processing table A, and digit span forward and backward. Neuropsychometric dysfunction was defined as more than 1 SD deterioration in more than 2 neuropsychometric tests. Chi-square. tests, Fisher tests, t tests, and analysis of variance were used as appropriate for statistical analysis. Results: Group A had a significant postoperative increase in the inflammatory markers Soluble E-selectin, CD 18, and heat shock protein 70. This was not observed in group B. Neuropsychometric dysfunction was also significantly higher in group A compared with group B. There was no difference in any other early postoperative clinical outcome. Conclusions: Our results seem to indicate that pretreatment with hyperbalic oxygen can reduce neuropsychometric dysfunction and also modulate the inflammatory response after cardiopulmonary bypass. However, further multicenter randomized trials are needed to clinically evaluate this form of therapy

Endothelial function and stress response after simulated dives to 18 msw breathing air or oxygen

Decompression sickness is caused by gas bubbles released upon decompression. These bubbles have the potential to occlude blood vessels and damage the vascular endothelium. The aim of this study was to quantify damage to the vascular endothelium resulting from decompression by measuring endothelial microparticles (MP) and endothelial function

Long-term exposure to traffic-related air pollution and lung cancer risk.

BACKGROUND: Most studies on the association between lung cancer and air pollution have investigated mortality. There have been few studies of lung cancer incidence. METHODS: We used data from the ongoing Netherlands Cohort Study on Diet and Cancer for 114,378 subjects with follow-up from September 1986 to December 1997. Exposure to black smoke, nitrogen dioxide (NO2), sulfur dioxide (SO2), and particulate matter < or =2.5 microm (PM2.5) and traffic intensity variables (intensity on nearest road, intensity in a 100 m buffer, and an indicator variable for living close to a major road) were estimated at the home address. We conducted Cox proportional hazard analyses in the full cohort adjusting for age, sex, smoking status, and area-level socioeconomic status. We also carried out case-cohort analyses using more potential confounders on a subset of study participants for whom complete information from the baseline questionnaire had been processed. RESULTS: Adjusted analyses included 1940 cases for the full cohort and 1295 cases for the case-cohort analysis. Relative risks (RRs) for the overall air pollution concentrations were slightly below unity, and for the traffic variables RRs were slightly elevated. Risk was elevated among people who never smoked cigarettes (40,114 participants; 252 cases), with RRs of 1.47 (95% confidence interval = 1.01-2.16) for overall black smoke concentration, 1.11 (0.88-1.41) for traffic intensity on nearest road, and 1.55 (0.98-2.43) for living near a major road. CONCLUSIONS: We found evidence for an association of exposure to black smoke and traffic with lung cancer incidence in people who had never smoked. No associations were found for the full cohort, or for other categories of smoking