Teprasiran, a Small Interfering RNA, for the Prevention of Acute Kidney Injury in High-Risk Patients Undergoing Cardiac Surgery: A Randomized Clinical Study.

Background: Acute kidney injury (AKI) affects up to 30% of patients undergoing cardiac surgery, leading to increased in-hospital and long-term morbidity and mortality. Teprasiran is a novel small interfering RNA that temporarily inhibits p53-mediated cell death that underlies AKI.

Methods: This prospective, multicenter, double-blind, randomized, controlled phase 2 trial evaluated the efficacy and safety of a single 10 mg/kg dose of teprasiran versus placebo (1:1), in reducing the incidence, severity, and duration of AKI after cardiac surgery in high-risk patients.

Safety and Tolerability Study of an Intravenously Administered Small Interfering Ribonucleic Acid (siRNA) Post On-Pump Cardiothoracic Surgery in Patients at Risk of Acute Kidney Injury.

Introduction: Patients undergoing on-pump cardiac surgery are at an increased risk of acute kidney injury. QPI-1002, a small interfering ribonucleic acid, is under clinical development for the prevention of acute kidney injury. The safety, tolerability, and pharmacokinetics of QPI-1002 was evaluated in this first-in-man, Phase 1 study of a small, interfering ribonucleic acid in patients at risk of acute kidney injury after on-pump cardiac surgery.

rPSGL-Ig for improvement of early liver allograft function: a double-blind, placebo-controlled, single-center phase II study.

The selectin antagonist known as recombinant P-selectin glycoprotein ligand IgG (rPSGL-Ig) blocks leukocyte adhesion and protects against transplantation ischemia reperfusion injury (IRI) in animal models. This randomized (1:1) single-center double-blind 47-patient phase 2 study with 6-month follow-up assessed rPSGL-Ig's safety and impact on early graft function at 1 mg/kg systemic dose with pretransplant allograft ex vivo treatment in deceased-donor liver transplant recipients. Safety was assessed in all patients, whereas efficacy was assessed in a prospectively defined per-protocol patient set (PP) by peak serum transaminase (TA) and bilirubin values, and normalization thereof.

YSPSL (rPSGL-Ig) for improvement of early renal allograft function: a double-blind, placebo-controlled, multi-center Phase IIa study.

Introduction: Recombinant P-selectin glycoprotein ligand IgG fusion protein, rPSGL-Ig (YSPSL), a fusion protein of human P-selectin ligand and IgG1-Fc, blocks leukocyte adhesion and protects against ischemia reperfusion injury (IRI) in animal models.

Patients And Methods: This randomized 15-center, double-blind, 59-patient Ph2a study assessed YSPSL's safety in recipients of deceased-donor kidney allografts and its potential efficacy in improving early graft function. Two doses and two dosing modalities were evaluated.

Autologous hematopoietic stem cell transplantation for type 1 diabetes.

In this review, we present (1) the scientific basis for the use of high-dose immunosuppression followed by autologous peripheral blood hematopoietic stem cell transplantation for newly diagnosed type 1 diabetes (T1D); (2) an update of the clinical and laboratory outcome of 20 patients transplanted at the University Hospital of the Ribeirão Preto Medical School, University of São Paulo, Brazil, and followed up to January/2008, including 4 relapses among 19 patients without previous ketoacidosis; (3) a commentary on criticisms to our article that appeared in four articles from the scientific literature; and (4) a discussion of the prospectives for cellular therapy for T1D.

Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus.

Context: Type 1 diabetes mellitus (DM) results from a cell-mediated autoimmune attack against pancreatic beta cells. Previous animal and clinical studies suggest that moderate immunosuppression in newly diagnosed type 1 DM can prevent further loss of insulin production and can reduce insulin needs.

Objective: To determine the safety and metabolic effects of high-dose immunosuppression followed by autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) in newly diagnosed type 1 DM.

Inferring colonization history from analyses of spatial genetic structure within populations of Pinus strobus and Quercus rubra.

Many factors interact to determine genetic structure within populations including adult density, the mating system, colonization history, natural selection, and the mechanism and spatial patterns of gene dispersal. We examined spatial genetic structure within colonizing populations of Quercus rubra seedlings and Pinus strobus juveniles and adults in an aspen-white pine forest in northern Michigan, USA. A 20-year spatially explicit demographic study of the forest enables us to interpret the results in light of recent colonization of the site for both species.

An individual bioequivalence approach to compare the intrasubject variability of two ciclosporin formulations, SangCya and Neoral.

A novel bioequivalence testing approach was used to determine intrasubject variability and switchability of two ciclosporin formulations, SangCya (test) and Neoral (reference). Twenty healthy volunteers were enrolled into a single-dose, randomized, open-label, 4-period, 2-sequence study with a crossover replicate design. Subject-by-formulation interaction variances were compared using a mixed effects linear model.

Prolongation of porcine islet xenograft survival in mice after therapy with immunosuppressive peptides.

Background: Recently, peptides derived from the heavy chain of HLA-B2702 have been shown to modulate immune responses. In this study, we examined the use of these peptides for immunosuppression in a pig to mouse islet xenograft model.

Methods: Purified porcine islets were transplanted in autoimmune (non-obese diabetic) and non-autoimmune (streptozotocin-injected CBA or C57/Bl6) diabetic mice.

Results of the double-blind, randomized, multicenter, phase III clinical trial of Thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation.

Background: Thymoglobulin, a rabbit anti-human thymocyte globulin, was compared with Atgam, a horse anti-human thymocyte globulin for the treatment of acute rejection after renal transplantation.

Methods: A multicenter, double-blind, randomized trial with enrollment stratification based on standardized histology (Banff grading) was conducted. Subjects received 7-14 days of Thymoglobulin (1.

Large granular lymphocyte leukaemia occurring after renal transplantation.

Post-transplantation lymphoproliferative disorders (PTLD) are a clinicopathologically heterogeneous group of lymphoid proliferations. The majority are of B-cell origin and associated with Epstein-Barr virus (EBV) infection. In contrast, the development of T-cell PTLD is much less common and EBV does not appear to be involved in pathogenesis.

Adenovirus infection of the renal allograft with sparing of pancreas graft function in the recipient of a combined kidney-pancreas transplant.

We report a case of adenovirus infection of the renal allograft in a combined kidney/pancreas transplant recipient. The clinical presentation was renal allograft failure, which eventually reversed. The pancreatic graft function remained stable.

Augmenter of liver regeneration enhances the success rate of fetal pancreas transplantation in rodents.

Background: Treatment of fetal pancreas (FP) isografts with insulin-like growth factor-I greatly improves the rate of conversion to euglycemia in diabetic rats. Complete knowledge of other factors that may facilitate the engraftment and function of FP in vivo is still embryonic. Augmenter of liver regeneration (ALR) is a newly described polypeptide growth factor found in weanling rat livers.

Survival of rat small bowel allografts treated with allotrap 07R.

Previous reports from other investigators demonstrate prolongation of allogeneic heart graft survival and decrease in CTL responses in rats treated with a small synthetic peptide corresponding to residues 75-84 of the human HLA-B7-01 molecule (Allotrap 07R). We wished to determine the efficacy of these peptides in the highly immunogenic ACI > LEW and LEW > ACI small bowel transplant models. Animals were divided into treatment groups: I, none; II, Allotrap (20 mg/kg/day on Days 0-4); III, cyclosporine (CsA; 10 mg/kg/day on Days 0-4); IV, Allotrap + CsA (as in groups II and III); V, Allotrap (40 mg/kg/day every other day on Days -19 to 4); VI, Allotrap + CsA (as in groups III and V); VII, Allotrap + CsA (as in groups III and V, with Allotrap administered intragraft Days 0-4).

Regimens of IGF-I treatment in fetal pancreas transplantation.

Transplantation of fetal pancreas (FP) is a potential treatment for diabetes mellitus. FP has remarkable proliferative capacity and may be induced to expand sufficiently to provide a functional beta cell mass in adult recipients. We have demonstrated that local delivery of recombinant insulin-like growth factor-I (IGF-I) onto FP isografts is sufficient to reverse streptozotocin-induced diabetes in animals receiving as few as 4 fetal pancreata.

Kupffer cells can present alloantigen in vitro: an effect abrogated by gadolinium.

Portal venous (PV) injection of alloantigen can result in tolerance. We have previously reported that this effect is abrogated by pretreatment with gadolinium (Gd), an element known to inhibit Kupffer cell phagocytosis. To further elucidate the role of Kupffer cells (KC) in PV tolerance, the present study examined the ability of KC to present alloantigen in vitro to syngeneic responder lymphocytes after in vivo PV administration of alloantigen with or without pretreatment with Gd.

Length of time on dialysis prior to renal transplantation is a critical factor affecting patient survival after allografting.

Within the past year at our transplant center we have had the experience of performing renal allografts in two patients older than 65 years, each of whom had been on hemodialysis more than 10 years. Both resulted in patient mortality within 90 days of transplant (one due to myocardial infarction, the other due to visceral ischemia with infarction). This prompted us to review retrospectively our own data (n = 204) and the national (UNOS) data (n = 10,971) regarding transplant outcome, patient age, and length of time on dialysis prior to renal transplantation.