Organ transplantation has developed over the past 50 years to reach the sophisticated and integrated clinical service of today through several advances in science. One of the most important of these has been the ability to apply organ preservation protocols to deliver donor organs of high quality, via a network of organ exchange to match the most suitable recipient patient to the best available organ, capable of rapid resumption of life-sustaining function in the recipient patient. This has only been possible by amassing a good understanding of the potential effects of hypoxic injury on donated organs, and how to prevent these by applying organ preservation. This review sets out the history of organ preservation, how applications of hypothermia have become central to the process, and what the current status is for the range of solid organs commonly transplanted. The science of organ preservation is constantly being updated with new knowledge and ideas, and the review also discusses what innovations are coming close to clinical reality to meet the growing demands for high quality organs in transplantation over the next few years.
Organ preservation has been of major importance ever since transplantation developed into a global clinical activity. The relatively simple procedures were developed on a basic comprehension of low-temperature biology as related to organs outside the body. In the past decade, there has been a significant increase in knowledge of the sequelae of effects in preserved organs, and how dynamic intervention by perfusion can be used to mitigate injury and improve the quality of the donated organs. The present review focuses on (1) new information about the cell and molecular events impacting on ischemia/reperfusion injury during organ preservation, (2) strategies which use varied compositions and additives in organ preservation solutions to deal with these, (3) clear definitions of the developing protocols for dynamic organ perfusion preservation, (4) information on how the choice of perfusion solutions can impact on desired attributes of dynamic organ perfusion, and (5) summary and future horizons.
Recent evidences indicate new roles for the glycolytic protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in essential mammalian cell processes, such as apoptosis and proliferation. To clarify the involvement of this protein in growth and programmed cell death in the liver, cell models of hepatocytes in culture were used to study GAPDH expression, localization and enzymatic activity in hepatocyte proliferation and apoptosis. GAPDH expression in cell compartments was studied by Western blot. Nuclear expression of GAPDH increased in apoptosis, and cytoplasmic expression was elevated in apoptosis and proliferation. Subcellular localization was determined by GAPDH immunostaining and confocal microscopic analysis. Quiescent and proliferating hepatocytes showed cytoplasmic GAPDH, while apoptotic cells showed cytoplasmic but also some nuclear staining. The glycolytic activity of GAPDH was studied in nuclear and cytoplasmic cell compartments. GAPDH enzymatic activity increased in the nucleus of apoptotic cells and in cytoplasms of apoptotic and proliferating hepatocytes. Our observations indicate that during hepatocyte apoptosis GAPDH translocates to the nucleus, maintaining in part its dehydrogenase activity, and suggest that this translocation may play a role in programmed hepatocyte death. GAPDH over-expression and the increased enzymatic activity in proliferating cells, with preservation of its cytoplasmic localization, would occur in response to the elevated energy requirements of dividing hepatocytes. In conclusion, GAPDH plays different roles or biological activities in proliferating and apoptotic hepatocytes, according to its subcellular localization.
Abstract. We report important results of the ®rst campaign specially designed to observe the formation and the initial convection of polar cap patches. The principal instrumentation used in the experiments comprised the EISCAT, the Sondrestrom, and the Super DARN network of radars. The experiment was conducted on February 18, 1996 and was complemented with additional sensors such as the Greenland chain of magnetometers and the WIND and IMP-8 satellites. Two dierent types of events were seen on this day, and in both events the Sondrestrom radar registered the formation and evolution of large-scale density structures. The ®rst event consisted of the passage of traveling convection vortices (TCV). The other event occurred in association with the development of large plasma jets (LPJ) embedded in the sunward convection part of the dusk cell. TCVs were measured, principally, with the magnetometers located in Greenland, but were also con®rmed by the line-of-sight velocities from the Sondrestrom and SuperDARN radars. We found that when the magnetic perturbations associated with the TCVs were larger than 100 nT, then a section of the high-latitude plasma density was eroded by a factor of 2. We suggest that the number density reduction was caused by an enhancement in the O + recombination due to an elevated T i , which was produced by the much higher frictional heating inside the vortex. The large plasma jets had a considerable (>1000 km) longitudinal extension and were 200±300 km in width. They were seen principally with the Sondrestrom, and Super-DARN radars. Enhanced ion temperature (T i ) was also observed by the Sondrestrom and EISCAT radars. These channels of high T i were exactly collocated with the LPJs and some of them with regions of eroded plasma number density. We suggest that the LPJs bring less dense plasma from later local times. However, the recent time history of the plasma¯ow is important to de®ne the depth of the density depletion. Systematic changes in the latitudinal location and in the intensity of the LPJs were observed in the 2 min time resolution data of the SuperDARN radars. The eect of the abrupt changes in the LPJs location is to create regions containing dayside plasma almost detached from the rest of the oval density. One of these density features was seen by the Sondrestrom radar at 1542 UT. The data presented here suggest that two plasma structuring mechanisms (TCVs and LPJs) can act tens of minutes apart to produce higher levels of density structures in the near noon F-region ionosphere.
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