Issues In Clinical Transplantation Research Articles

Caffeic acid attenuates rat liver injury after transplantation involving PDIA3-dependent regulation of NADPH oxidase

The transplanted liver inevitably suffers from ischemia reperfusion (I/R) injury, which represents a key issue in clinical transplantation determining early outcome and long-term graft survival. A solution is needed to deal with this insult. This study was undertaken to explore the effect of Caffeic acid (CA), a naturally occurring antioxidant, on I/R injury of grafted liver and the mechanisms involved. Male Sprague–Dawley rats underwent orthotopic liver transplantation (LT) in the absence or presence of CA administration. In vitro, HL7702 cells were subjected to hypoxia/reoxygenation. LT led to apparent hepatic I/R injury, manifested by deteriorated liver function, microcirculatory disturbance and increased apoptosis, along with increased PDIA3 expression and nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase activity, and membrane translocation of NADPH oxidase subunits. Treatment with CA attenuated the above alterations. siRNA/shRNA-mediated knockdown of PDIA3 in HL7702 cells and rats played the same role as CA not only in inhibiting ROS production and NADPH oxidase activity, but also in alleviating hepatocytes injury. CA protects transplanted livers from injury, which is likely attributed to its protection of oxidative damage by interfering in PDIA3-dependent activation of NADPH oxidase.

Grief and loss for patients before and after heart transplant

ObjectivesThe purpose of the study was to examine the loss and grief experiences of patients waiting for and living with new hearts. BackgroundThere is much scholarship on loss and grief. Less attention has been paid to these issues in clinical transplantation, and even less on the patient experience. MethodsPart of a qualitative inquiry oriented to the work of Merleau-Ponty, a secondary analysis was carried out on audiovisual data from interviews with thirty participants. ResultsPatients experience loss and three forms of grief. Pre-transplant patients waiting for transplant experience loss and anticipatory grief related to their own death and the future death of their donor. Transplanted patients experience long-lasting complicated grief with respect to the donor and disenfranchised grief which may not be sanctioned. ConclusionsLoss as well as anticipatory, complicated and disenfranchised grief may have been inadvertently disregarded or downplayed. More research and attention is needed.

Long term cryostorage of UC blood units: ability of the integral segment to confirm both identity and hematopoietic potential

With the maturation of UC blood banking, cord blood (CB) units stored for years prior to use in transplantation present a new set of issues in clinical transplantation, including interval improvements in immune typing and confirmation of product identity and viability. A preliminary analysis of the transplants supported by the St Louis Cord Blood Bank, looking for an impact of length of CB storage time and transplant outcome was performed. We evaluated the utility of an integral segment containing an aliquot of cryopreserved product that has been exposed to the same post-processing storage conditions as the unit as a quality control tool for CB banking. Engraftment and survival following unrelated donor UC blood transplant were evaluated based on length of CB product storage at the St Louis Cord Blood Bank. A strategy of routine testing of the contiguous segment for high-resolution HLA typing (also confirming identity) and CFU analysis was tested in 283 consecutive CB searches. Comparison between CB unit and contiguous segment viability and hematopoietic potential was performed on 30 research CB units that had been stored up to 5 years. There was no statistical difference in engraftment or survival following unrelated donor cord blood transplant employing units banked < 1 year or > 3 years. Confirmatory HLA typing, CFU and viability testing was successfully performed from the same segment as part of a strategy for product release evaluation. When comparing the segment with its corresponding CB unit, the total colony-forming units (CFU) measured in the two was similar (P = 0.51, paired t-test). Three research units purposely sabotaged by an overnight thaw and refreeze had no CFU growth, but viability as measured by Trypan was still 68-98%. No deterioration of hematopoietic potential has been detected with storage up to 5 years. The contiguous segment CFU is representative of the product, and thus is a useful tool for quality control and confirmation of product viability. Viability, as measured by Trypan blue dye exclusion may be falsely reassuring.

Discriminating rejection from CMV infection in renal allograft recipients using flow cytometry

The ability to distinguish among rejection, cytomegalovirus (CMV) infection, and cyclosporin toxicity in the symptomatic renal allograft recipient remains one of the major issues in clinical transplantation. The practical application of immunologic monitoring of peripheral blood lymphocytes through the use of fluorescently labeled monoclonal antibodies and single-color flow cytometry has been limited by the inability to demonstrate significant correlations between the levels of specific T-cell subset populations and the cause of impaired renal function. In the present study using two-color analysis, we monitored the expression of interleukin-2 receptor (IL-2R) and HLA-DR antigen on the T-cells of a group of 51 renal cadaveric allograft recipients receiving cyclosporin, azathioprine, and prednisone for an average of 4 months after transplantation. We found that the proportion of CD3 + cells coexpressing IL-2R increased above baseline during 12 out of 14 rejection episodes that took place during the course of the study ( P < 10 −6). Alternatively, we found that the proportion of cells coexpressing HLA-DR antigen on CD2 + cells increased above baseline during 11 out of 11 CMV infections ( P < 10 −6). There was no correlation between the level of IL-2R + CD3 + cells and CMV infection or between the level of CD2 + DR + cells and rejection. These relationships showed a high degree of sensitivity and specificity when used to discriminate among possible etiologies for decreased renal function in the symptomatic patient.