Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014118 (endocarditis)
 15,629 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac tissues show a propensity to develop nonbacterial thrombotic endocarditis, a meshwork of platelets and fibrin. This lesion may cause a predisposition to subsequent colonization by circulating microorganisms, leading to infective endocarditis. We measured platelet adherence in vitro to cultured endothelial cells derived from the porcine aortic valve and ascending aorta. We found that valvular endothelial cells showed a twofold to threefold higher adherence than ascending aortic endothelial cells of chromium 51-labeled platelets in the presence of proteolytically active thrombin. This finding did not correlate with endothelial prostacyclin release: cardiac valve endothelial cells released more prostacyclin than did, ascending aortic cells, exogenous prostacyclin had no effect on thrombin-stimulated adherence, and aspirin inhibition of endothelial prostacyclin synthesis showed no effect on platelet adherence. Fixation of platelets abolished thrombin-stimulated adherence; fixation of endothelial cells had minimal effect. We suggest that these differences may contribute to the propensity of the cardiac valve to develop nonbacterial thrombotic endocarditis.
 ...
PMID:Platelet adherence to cardiac and noncardiac endothelial cells in culture: lack of a prostacyclin effect. 304 33

In a proposed study of fibrinolytic therapy in experimental streptococcal endocarditis, this disease was induced in pigs by preinoculation damage to the aortic valve; the technique of this is described. If untreated, the disease runs a protracted course, similar to that in man. Fibrinolytic activity, normally low in the pig, can be increased by stress, by urokinase, by plasmin and briefly by streptokinase if supplemented by human plasminogen. The proposed experiments were abandoned in pigs, chiefly because of technical difficulties in obtaining frequent samples of blood and maintaining infusions. In experiments on the response of ADP-induced aggregation of pig platelets to prostacyclin, they were found to be about 10 times more resistant than human platelets. It is suggested that this resistance to prostacyclin, together with their usually low state of systemic fibrinolytic activity, may explain the susceptibility of pigs to bacterial endocarditis.
 ...
PMID:A study of experimental endocarditis in pigs. 331 15

Platelet aggregation by bacteria is felt to play an important role in the pathogenesis of infective endocarditis. However, the mechanisms involved in bacterium-induced platelet aggregation are not well-defined. In the present study, we examined the mechanisms by which Staphylococcus aureus causes rabbit platelet aggregation in vitro. In normal plasma, the kinetics of S. aureus-induced platelet aggregation were rapid and biphasic. The onset and magnitude of aggregation phase 1 varied with the bacterium-platelet ratio, with maximal aggregation observed at a ratio of 5:1. The onset of aggregation phase 2 was delayed in the presence of apyrase (an ADP hydrolase), suggesting that this later aggregation phase may be triggered by secreted ADP. The onset of aggregation phase 2 was delayed in the presence of prostaglandin I2-treated platelets, and this phase was absent when paraformaldehyde-fixed platelets were used, implicating platelet activation in this process. Platelet aggregation phase 2 was dependent on S. aureus viability and an intact bacterial cell wall, and it was mitigated by antibody directed against staphylococcal clumping factor (a fibrinogen-binding protein) and by the cyclooxygenase inhibitor indomethacin. Similarly, aggregation phase 2 was either delayed or absent in three distinct transposon-induced S. aureus mutants with reduced capacities to bind fibrinogen in vitro. In addition, a synthetic pentadecapeptide, corresponding to the staphylococcal binding domain in the C terminus of the fibrinogen delta-chain, blocked aggregation phase 2. However, phase 2 of aggregation was not inhibited by two synthetic peptides (alone or in combination) analogous to the two principal fibrinogen-binding domains on the platelet glycoprotein (GP) IIb/IIIa integrin receptor: (i) a recognition site on the IIIa molecule for the Arg-Gly-Asp (RGD) sequence of the fibrinogen alpha-chain and (ii) a recognition site on the IIb molecule for a dodecapeptide sequence of the fibrinogen delta-chain. This differs from ADP-induced platelet aggregation, which relies on an intact platelet GP IIb/IIIa receptor with an accessible RGD sequence and dodecapeptide recognition site for fibrinogen. Furthermore, a monoclonal antibody directed against the RGD recognition site on rabbit platelet GP IIb/IIIa receptors failed to inhibit rabbit platelet aggregation by S. aureus. Collectively, these data suggest that S. aureus-induced platelet aggregation requires bacterial binding to fibrinogen but is not principally dependent upon the two major fibrinogen-binding domains on the platelet GP IIb/IIIa integrin receptor, the RGD and dodecapeptide recognition sites.
 ...
PMID:Staphylococcus aureus induces platelet aggregation via a fibrinogen-dependent mechanism which is independent of principal platelet glycoprotein IIb/IIIa fibrinogen-binding domains. 764 1

We describe a 46-year-old man who developed infective endocarditis, meningitis, sternal abscess, and infective cerebral emboli after cardiac transplantation. Staphylococcus aureus was the infective organism. We successfully managed the patient with flucloxacillin and fusidic acid to treat infection, and with prostacyclin for systemic embolization.
 ...
PMID:Bacterial endocarditis: a rare complication following orthotopic cardiac transplantation. 1129 87