Continuous positive airway pressure and platelet activation in obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is a complex condition associated with a number of cardiovascular sequelae including hypertension (both systemic and pulmonary), congestive heart failure, arrhythmias, myocardial infarction and stroke [1-6]. However, the recent American Heart Association/American College of Cardiology scientific statement on sleep apnoea suggests that there is a paucity of data for a causal role of OSA in cardiovascular disease [7] which underlines the importance of studies such as that of Akinnusi and co-workers in this edition of Respiration that are aimed at understanding the pathophysiology of OSA[8]

Platelet-Bacterial Interactions as Therapeutic Targets in Infective Endocarditis

Endocarditis is an inflammation of the lining of the heart and valves. It can be due to a noninfectious cause (Asopa et al., 2007) but when the inflammation is associated with an infection, usually bacterial, it is known as infective endocarditis (IE) and is characterized by the development of a large septic thrombus on one of the cardiac valves (Beynon et al., 2006; Moreillon and Que, 2004). As this thrombus grows, it can lead to valve failure or may fragment forming a septic embolus that is associated with high mortality if the target of the embolus is the brain, heart or lung (Homma and Grahame-Clarke, 2003). Untreated the mortality is very high and even with aggressive therapy with antibiotics and valve replacement surgery there is a significant mortality. Primarily the disease is due to the formation of a platelet-bacteria thrombus on a cardiac valve and this review will look at the interaction between bacteria and platelets within the context of endocarditis

Immunological and toxicological studies on drugs and blood coagulation factors

1) Monoclonal antibodies directed against both Factor FVIII procoagulant protein (FVIII C) and fibrinogen were produced and characterised. 2) Polyclonal antisera directed against a BSA-diazepam conjugate was produced These were found to be directed against the conjugate rather than diazepam. 3) IB vitro studies on the effects of both coumarin and 7 -hydroxycoumarin on the growth of cells indicated that neither drug was cytotoxic, but they both slowed the growth of cells in vitro 7-hydroxycoumarm was found to have more potent cytostatic effects than coumarin. 4) The results from a clinical study on the effects of coumarin on liver function indicated that 0 36% of patients experienced an idiosyncratic hepatotoxicity to coumarin

Characterisation of the genome of Nudaurelia Omega Virus

Nudaurelia co virus (Nco V) is a small RNA virus belonging to the Family Tetraviridae. Nco V was successfully isolated from field collected larvae of the pine emperor moth, Nudaurelia cytherea capensis. By polyacrylamide gel electrophoresis-it was possible Jo determine the size of the capsid proteins. Anti-NcoV antiserum was raised by inoculating a rabbit with purified virus. RNA was extracted from the purified virus using a phenol\chloroform extraction procedure. It was possible to separate the viral RNA into its constituent species using sucrose density gradient centrifugation. The sizes of both species of RNA was accurately determined by agarose gel electrophoresis. These sizes corresponded to the replicative form of the RNA which was extracted from infected host tissue. The absence of a poly(A) tract on the RNA was shown through poly(U) sepharose chromatography. Cell-free translation of the viral RNA elucidated the sizes of proteins encoded in vitro in a rabbit reticulocyte lysate system. Optimal conditions for in vitro translation of Nco V were determined for a range of conditions. Immunoprecipitaion of viral encoded proteins with anti-Nco V antiserum suggested that the putative coat protein of the virus was encoded by RNA 2, as a precursor polypeptide which underwent posttranslational cleavage. Reverse transcription - polymerase chain reaction (RT -PCR) was used to successfully produce a radiolabelled probe which could detect dot-blotted viral RNA. The efficacy of this probe in detecting the presence of Nco V RNA in infected tissue was also tested

Sepsis – it is all about the platelets

Sepsis is accompanied by thrombocytopenia and the severity of the thrombocytopenia is associated with mortality. This thrombocytopenia is characteristic of disseminated intravascular coagulation (DIC), the sepsis-associated coagulopathy. Many of the pathogens, both bacterial and viral, that cause sepsis also directly activate platelets, which suggests that pathogen-induced platelet activation leads to systemic thrombosis and drives the multi-organ failure of DIC. In this paper we review the mechanisms of platelet activation by pathogens and the evidence for a role for anti-platelet agents in the management of sepsis

Human platelet activation by Escherichia coli: roles for FcγRIIA and integrin αIIbβ3

Gram-negative Escherichia coli cause diseases such as sepsis and hemolytic uremic syndrome in which thrombotic disorders can be found. Direct platelet–bacterium interactions might contribute to some of these conditions; however, mechanisms of human platelet activation by E. coli leading to thrombus formation are poorly understood. While the IgG receptor FcγRIIA has a key role in platelet response to various Gram-positive species, its role in activation to Gram-negative bacteria is poorly defined. This study aimed to investigate the molecular mechanisms of human platelet activation by E. coli, including the potential role of FcγRIIA. Using light-transmission aggregometry, measurements of ATP release and tyrosine-phosphorylation, we investigated the ability of two E. coli clinical isolates to activate platelets in plasma, in the presence or absence of specific receptors and signaling inhibitors. Aggregation assays with washed platelets supplemented with IgGs were performed to evaluate the requirement of this plasma component in activation. We found a critical role for the immune receptor FcγRIIA, αIIbβ3, and Src and Syk tyrosine kinases in platelet activation in response to E. coli. IgG and αIIbβ3 engagement was required for FcγRIIA activation. Moreover, feedback mediators adenosine 5’-diphosphate (ADP) and thromboxane A₂ (TxA₂) were essential for platelet aggregation. These findings suggest that human platelet responses to E. coli isolates are similar to those induced by Gram-positive organisms. Our observations support the existence of a central FcγRIIA-mediated pathway by which human platelets respond to both Gram-negative and Gram-positive bacteria

The Role of Platelets in Viral Hemorrhagic Fevers

Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae are all RNA viruses that can induce a coagulopathy in infected patients. While there is a paucity of information on the cause of this coagulopathy, these viruses all produce a severe thrombocytopenia. Here, we review the literature on viral hemorrhagic fever and discuss the role played by platelets in the coagulopathy. We also discuss the possibility of using anti-platelet agents to moderate the coagulopathy, a strategy that might have a role to play in treating patients infected by these viruses

C-reactive protein binds to alphaIIbbeta3.

C-reactive protein binds to alphaIIbbeta3