Impact of Normothermic Preservation with Extracellular Type Solution Containing Trehalose on Rat Kidney Grafting from a Cardiac Death Donor

BACKGROUND: The aim of this study was to investigate factors that may improve the condition of a marginal kidney preserved with a normothermic solution following cardiac death (CD) in a model of rat kidney transplantation (RTx). METHODS: Post-euthanasia, Lewis (LEW) donor rats were left for 1 h in a 23°C room. These critical kidney grafts were preserved in University of Wisconsin (UW), lactate Ringer's (LR), or extracellular-trehalose-Kyoto (ETK) solution, followed by intracellular-trehalose-Kyoto (ITK) solution at 4, 23, or 37°C for another 1 h, and finally transplanted into bilaterally nephrectomized LEW recipient rats (n = 4-6). Grafts of rats surviving to day 14 after RTx were evaluated by histopathological examination. The energy activity of these marginal rat kidneys was measured by high-performance liquid chromatography (HPLC; n = 4 per group) and fluorescence intensity assay (n = 6 per group) after preservation with UW or ETK solutions at each temperature. Finally, the transplanted kidney was assessed by an in vivo luciferase imaging system (n = 2). RESULTS: Using the 1-h normothermic preservation of post-CD kidneys, five out of six recipients in the ETK group survived until 14 days, in contrast to zero out of six in the UW group (p<0.01). Preservation with ITK rather than ETK at 23°C tended to have an inferior effect on recipient survival (p = 0.12). Energy activities of the fresh donor kidneys decreased in a temperature-dependent manner, while those of post-CD kidneys remained at the lower level. ETK was superior to UW in protecting against edema of the post-CD kidneys at the higher temperature. Luminescence intensity of successful grafts recovered within 1 h, while the intensity of grafts of deceased recipients did not change at 1 h post-reperfusion. CONCLUSIONS: Normothermic storage with extracellular-type solution containing trehalose might prevent reperfusion injury due to temperature-dependent tissue edema

Am J Prev Med

CC999999/Intramural CDC HHS/United States2017-02-19T00:00:00Z26456878PMC531651

History of clinical transplantation

How transplantation came to be a clinical discipline can be pieced together by perusing two volumes of reminiscences collected by Paul I. Terasaki in 1991-1992 from many of the persons who were directly involved. One volume was devoted to the discovery of the major histocompatibility complex (MHC), with particular reference to the human leukocyte antigens (HLAs) that are widely used today for tissue matching.1 The other focused on milestones in the development of clinical transplantation.2 All the contributions described in both volumes can be traced back in one way or other to the demonstration in the mid-1940s by Peter Brian Medawar that the rejection of allografts is an immunological phenomenon.3,4 © 2008 Springer New York

History of clinical transplantation

The emergence of transplantation has seen the development of increasingly potent immunosuppressive agents, progressively better methods of tissue and organ preservation, refinements in histocompatibility matching, and numerous innovations is surgical techniques. Such efforts in combination ultimately made it possible to successfully engraft all of the organs and bone marrow cells in humans. At a more fundamental level, however, the transplantation enterprise hinged on two seminal turning points. The first was the recognition by Billingham, Brent, and Medawar in 1953 that it was possible to induce chimerism-associated neonatal tolerance deliberately. This discovery escalated over the next 15 years to the first successful bone marrow transplantations in humans in 1968. The second turning point was the demonstration during the early 1960s that canine and human organ allografts could self-induce tolerance with the aid of immunosuppression. By the end of 1962, however, it had been incorrectly concluded that turning points one and two involved different immune mechanisms. The error was not corrected until well into the 1990s. In this historical account, the vast literature that sprang up during the intervening 30 years has been summarized. Although admirably documenting empiric progress in clinical transplantation, its failure to explain organ allograft acceptance predestined organ recipients to lifetime immunosuppression and precluded fundamental changes in the treatment policies. After it was discovered in 1992 that long-surviving organ transplant recipient had persistent microchimerism, it was possible to see the mechanistic commonality of organ and bone marrow transplantation. A clarifying central principle of immunology could then be synthesized with which to guide efforts to induce tolerance systematically to human tissues and perhaps ultimately to xenografts

A practical route to long-chain non-natural &#945;,&#969;-diamino acids

An efficient method for the synthesis of long-chain \u3b1,\u3c9-diamino acids, starting from natural \u3b1-amino acids, has been developed. The long-chain skeleton has been generated through condensation between a protected aldehyde, derived from l-aspartic acid, and an ylide obtained from an \u3c9-hydroxy-alkyl phosphonium salt. After conversion of the \u3c9-hydroxy group into an amine, catalytic hydrogenation produced the N, N\u2032-protected \u3b1,\u3c9-diamino acid. The present route to \u3b1,\u3c9-diamino acids allows the modulation of the chain length depending on the length of the ylide used for the Wittig olefination reaction

Synthesis of photoactivable probes for the study of glycosphingolipid-protein interactions

SYNTHESIS OF PHOTOACTIVABLE PROBES FOR THE STUDY OF GLYCOSPHINGOLIPID-PROTEIN INTERACTIONS Giuseppina Brasile,1 Federica Compostella,1 Laura Mauri,2Sandro Sonnino2 and Fiamma Ronchetti1 Dipartimento di Chimica, Biochimica e Biotecnologie per la Medicina, Universit\ue0 di Milano 1Via Saldini 50, 20133-Milano, Italy; 2Via Fratelli Cervi 93, 20190- Segrate (Milano), Italy E-mail:[email protected] It is widely accepted that glycosphingolipids (GSLs) at the level of the plasma membrane can affect the biological functions of protein molecules, such as cell surface receptors or transporters. The interactions between GSLs and proteins belonging to specific membrane microdomains, called lipid rafts, could be responsible for the modulation of the functional properties of membrane proteins participating in signal transduction. GSL-protein interactions can be investigated by cell photolabelling experiments using radioactive photoactivable GSLs, which yield, when illuminated, a very reactive intermediate that covalently binds to the molecules in the environment, i.e. proteins.1,2 In this context, we have designed a fatty acid probe with two nitrophenylazide photoactivable groups, one at position 2 and the other at the end of the acyl chain. The conjugation of the fatty acid to a radioactive sphingoglycolipid generates a species to be used for photolabelling experiments. In this way, the simultaneous identification of the proteins belonging to both the leaflets of the plasma membrane, the cytoplasmatic and the extracellular one, will be realized. Herein we describe a general synthetic strategy to obtain not commercially available \u3b1,\u3c9-diamino acids, the synthetic precursors of the labelled fatty acids, which we have applied to the synthesis of a C-18 derivative. Furthermore, it will be described the preparation of a photolabelled radioactive GSL as a case study. 1. Aureli M., Prioni S., Mauri L. Loberto N., Casellato R., Ciampa M.G., Chigorno V., Prinetti, A.; Sonnino S. J. Lipid Res. 2010, 51, 798-808 2. Mauri L., Prioni S., Loberto N., Chigorno V., Prinetti A., Sonnino S. Glycoconj. J. 2004, 20, 11-23