Extensive platelet activation in preeclampsia compared with normal pregnancy: enhanced expression of cell adhesion molecules

OBJECTIVES: Platelets play an important role in the pathophysiologic mechanisms of preeclampsia. Our purpose was to investigate by means of flow cytometry to what extent platelets circulate in an activated state during normal pregnancy and whether this activation is more extensive in preeclampsia. STUDY DESIGN: Platelets in whole blood from 10 preeclamptic third-trimester pregnant women (highest diastolic blood pressure range 100 to 130 mm Hg, proteinuria range 0.59 to 11.5 gm/24 hr) and from 10 normotensive third-trimester pregnant controls were analyzed with the following activation markers: anti-P-selectin (alpha-granule secretion), anti-CD63 (lysosomal secretion), PAC-1 (monoclonal antibody against fibrinogen receptor conformation of the glycoprotein IIb/IIIa complex), anti-platelet endothelial cell adhesion molecule-1, and annexin-V (a placental protein that binds to negatively charged phospholipids, present on the outside of the platelet plasma membrane after activation). The differences in surface antigen exposure between the two groups were determined by double-label flow cytometry. Flow cytometric data were analyzed in two ways: first, the percentages of activated platelets above a certain threshold compared with a nonpregnant control sample were determined, indicative for activation of a subpopulation of cells, and, second, the mean fluorescence intensities were determined, indicative of the mean surface antigen expression of the total platelet population. RESULTS: Analysis of the percentage of activated platelets proved most informative. With this analysis an enhanced platelet activation status was present in 4 of 10 normotensive patients and a more extensive platelet activation status in all 10 preeclamptic patients, as indicated by P-selectin (p = 0.008) and CD63 (p = 0.03) expression. Increased platelet endothelial cell adhesion molecule-1 (p = 0.005) expression was also observed in preeclampsia. CONCLUSIONS: Flow cytometric analysis clearly indicated that platelets circulate in a more extensively activated state during preeclampsia than during normal pregnancy. The increased platelet endothelial cell adhesion molecule-1 expression in preeclamptic patients demonstrates that, besides alpha-granular and lysosomal release, other hitherto unknown mechanisms are involved. Platelet endothelial cell adhesion molecule-1 appears to be the best marker to distinguish preeclamptic patients from normotensive pregnant women. Only a subpopulation of the platelets appears to be activated.     

Increased levels of plasma cholesteryl ester hydroperoxides in patients with subarachnoid hemorrhage

The pathophysiology of subarachnoid hemorrhage (SAH) may involve free radical production and lipid peroxidation. We examined plasma levels of cholesteryl ester hydroperoxides (CEOOH) and antioxidants in 25 patients with SAH, and 10 neurologic controls with lacunar stroke. Patients with SAH had significantly increased plasma levels of CEOOH, which peaked on day 5 after the ictus. Concentrations of CEOOH were significantly increased, and ascorbic acid concentrations were significantly decreased in patients who developed vasospasm compared with patients without vasospasm. Increased levels of CEOOH were associated with increased mortality and correlated with clinical outcome scales. These results implicate oxidative stress in the pathogenesis of SAH and suggest that measurements of CEOOH in plasma may be useful both prognostically as well as in monitoring therapeutic interventions.     

Lesions of the tracheobronchial tree after the aspiration of a tablet of ferrous sulfate

Foreign body aspiration requires emergency bronchoscopic examination when the product is chemically active. We describe the case of a female patient who aspirated a ferrous sulfate tablet that, in spite of being extracted immediately, caused lesions that persisted in the bronchial tree for 6 weeks. We then discuss the potential of ferrous sulfate substance to cause damage to the tracheobronchial tree.     

Activation of cysteine proteases in cowpea plants during the hypersensitive response--a form of programmed cell death

The matrix metalloproteinases appear to play a key role in mammary tissue remodeling during involution. By immunoprecipitation and immunoblot using antibodies against 60K gelatinase which appears during involution a 90K polypeptide has been identified as its inactive proenzyme in the early involuting rat mammary gland. 90K polypeptide was isolated from the second day involuting rat mammary gland by immunoaffinity chromatography. On proteolytic digestion, the inactive 90K polypeptide was converted to active gelatinase. Primary cultures of mammary epithelial cells secreted the 90K polypeptide. These results indicated that the 60K inducible MMP involved in mammary gland involution and remodeling is produced as a 90K proenzyme which is activated by proteolysis in the extracellular sites.