Activation platelets

Young s modulus for [CERAMICS - PffiCHANICAL PROPERTIES AND BEHAVIOR] (Vol 5) Platelet-activating factor QAE) antagonists... 

The synthetic utihty of the above transformations stems from the fact that many monoesters obtained as a result of hydrolysis may be converted to pharmaceutically important intermediates. For example, the optically active glycerol derivative (27) is a key intermediate in the production of P-blockers. Akyl derivative (25) may be converted into (5)-paraconic acid [4694-66-0] ((5)-5-oxo-3-tetrahydrofurancarboxyhc acid) that is a starting material for the synthesis of (3R)-A-factor. The unsaturated chiral cycHc monoacetate (31) is an optically active synthon for prostaglandins, and the monoester (29) is used for the synthesis of platelet activating factor (PAF) antagonists. 

Platelet Activating Factor A Potent Glyceroether Mediator... 

Platelet activating factor (PAF) was first identified by its ability (at low levels) to cause platelet aggregation and dilation of blood vessels, but it is now known to be a potent mediator in inflammation, allergic responses, and shock. PAF effects are observed at tissue concentrations as low as 10 M. PAF causes a dramatic inflammation of air passages and induces asthma-like symptoms in laboratory animals. Toxic-shock syndrome occurs when fragments of destroyed bacteria act as toxins and induce the synthesis of PAF. This results in a drop in blood pressure and a reduced... 

FIGURE 25.24 Platelet activating factor, formed from Talkyl-2-lysophosphatidylcholine by acetylation at C-2, is degraded by the action of acetylhydrolase. 

Various 1.4-benzodiazepines with a five-membered heteroaromatic ring fused to the 1,2-bond, such as 17, where A represents a heteroaromatic ring, have been prepared by such methods and tested for activity on the central nervous system, as cholecystokinin antagonists and as antagonists of platelet activating factors.245... 

Platelets play a central role in primary hemostasis. They are also important in pathological processes leading to thrombosis. Antiplatelet drugs are primarily directed against platelets and inhibit platelet activation by a number of different mechanisms. They are used for the prevention and treatment of thrombotic processes, especially in the arterial vascular system. 

The formation of a platelet aggregate requires the recruitment of additional platelets from the blood stream to the injured vessel wall. This process is executed through a variety of diffusible mediators which act through G-protein-coupled receptors. The main mediators involved in this process are adenosine diphosphate (ADP), thromboxane A2 (TXA2), and thrombin (factor Ila). These mediators of the second phase of platelet activation are formed in different ways. While ADP is secreted from platelets by exocytosis, the release of TXA2 follows its new formation in activated platelets. Thrombin can be formed on the surface of activated platelets (see Fig. 2). 

Most antiplatelet dtugs only partially inhibit platelet activation. In contrast, blockers of GPIIb/llla interfere at the end of the pathway common to platelet aggregation. They prevent fibrinogen and vWf from... 

The antiinflammatory effects of statins likely result from their ability to inhibit the formation of mevalonic acid. Downstream products of this molecule include not only the end product, cholesterol, but also several isoprenoid intermediates that covalently modify ( pre-nylate ) certain key intracellular signaling molecules. Statin treatment reduces leukocyte adhesion, accumulation of macrophages, MMPs, tissue factor, and other proinflammatory mediators. By acting on the MHC class II transactivator (CIITA), statins also interfere with antigen presentation and subsequent T-cell activation. Statin treatment can also limit platelet activation in some assays as well. All these results support the concept that in addition to their favorable effect on the lipid profile, statins can also exert an array of antiinflammatory and immunomodulatory actions. 

Collagen is a major component of connective tissue that becomes exposed at the subendothelium of injured blood vessels. It contributes to platelet adhesion and also plays a role in platelet activation by binding to several receptors on platelets such as integrin a 2(3 1 or glycoprotein VI (GP VI). 

Enterochromaffin cells are interspersed with mucosal cells mainly in the stomach and small intestine. In the blood, serotonin is present at high concentrations in platelets, which take up serotonin from the plasma by an active transport process. Serotonin is released on platelet activation. In the central nervous system, serotonin serves as a transmitter. The main serotonin-containing neurons are those clustered in form of the Raphe nuclei. Serotonin exerts its biological effects through the activation of specific receptors. Most of them are G-protein coupled receptors (GPCRs) and belong to the 5-HTr, 5-HT2-, 5-HT4-, 5-HTs-, 5-HT6-, 5-HT7-receptor subfamilies. The 5-HT3-receptor is a ligand-operated ion channel. 

Platelet-activating Factor Platelet Aggregation Inhibitors Platelet-derived Growth Factor Receptor Platelet Inhibitors Platelets... 

---