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The functions of the eukaryotic cell rely onmembrane-bound compartments called organelles. Each of these possesses distinct membrane composition and unique function. In the 1970’s, during George Palade’s time, it was unclear how these organelles communicate with each other and perform their biological functions. The elegant research work of James E Rothman, Randy W Schekman and Thomas C Südhof identified the molecular machinery required for membrane trafficking, vesicle fusion and cargo delivery. Further, they also showed the importance of these processes for biological function. Their novel findings helped to explain several biological phenomena such as insulin secretion, neuron communication and other cellular activities. In addition, their work provided clues to cures for several neurological, immunological and metabolic disorders. This research work laid the foundation to the field of molecular cell biology and these post-Palade investigators were awarded the Nobel Prize in Physiology or Medicine in 2013. 相似文献
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Rahat Kumar Narinder Singh Kartar Singh Atul Kalhan K. K. Prasad 《Indian journal of clinical biochemistry : IJCB》2004,19(1):122-128
The normal coagulation process is initiated by disruption and exposure of the subendothelial components of blood vessels.
Platelets adhere to subendothelium-bound von Willebrand factor via glycoprotein (GP) Ib complex. This initial interaction
per se and the release of platelet agonists transduce signals that leads to the rise in intracellular Ca2+ which induces shape
change, prostaglandin synthesis, release of granular contents and conformational changes in platelet Gp IIb-IIIa. Gp IIb-IIIa
in activated platelets binds fibrinogen and other adhesive proteins and mediates platelet cohesion the primary haemostatic
plug. Furthermore, the activated platelets due to aggregation, result in the formation of fibrin (secondary hemostasis). Normally
the haemostatic process plays a delicate balance between keeping the blood in the fluid state to maintain flow and rapidly
forming an occluding plug following vessel injury. Thrombosis occurs because of alteration in this delicate balance. Arterial
thrombosis occurs in the setting of previous vessel wall injury mostly because of atherosclerosis, while venous thrombosis
occurs in areas of stasis. The recent advances in understanding of the haemostatic process have led to a better understanding
of the mechanism of action of many antithrombotic drugs and identification of new targets for drug development. The molecular
target of the ticlopidine has been identified. Large numbers of IIb-IIIa inhibitors have been developed. The mechanism of
action of heparin has been defined at the molecular level. As a result, a synthetic pentasaccharide, based on antithrombin-binding
domain of heparin, has been developed and tested successfully in clinical trials. New generation direct thrombin inhibitors
are being developed. Factor Xa has a critical position at the convergence of intrinsic and extrinsic pathway. The clinical
tolerability and the efficacy of low molecular weight heparins has established that inhibition of further thrombin generation,
by blocking factor Xa alone can be an effective way of preventing thrombus growth without inactivating thrombin. A large number
of specific factor Xa inhibitors are under development. Some of these are in preliminary clinical trials and appear to be
promising. Future clinical trials will determine whether these new drugs will provide better risk-benefit ratio in treatment
of thrombotic disorders. Similarly role of thrombolytics has been clearly established in many diseases including coronary
artery disease. 相似文献
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