Anaphylaxis on reperfusion during liver transplantation with coagulopathy.

We present a case in which anaphylaxis on hepatic reperfusion during liver transplantation presented only with hypotension and coagulopathy. There were no cutaneous manifestations or clinical features distinguishing anaphylaxis from postreperfusion syndrome. The recipient regularly consumed seafood, and the organ donor died of anaphylaxis to shellfish.

Diagnostic accuracy of solid phase HLA antibody assays for prediction of crossmatch strength.

Solid phase antibody assays are increasingly used to provide quantitative measures of donor-specific HLA antibodies for assessment of pretransplant risk, although cell-based crossmatches continue to serve as gold standards for determination of donor HLA antibody strength. This study determined the ability of HLA antibody solid phase assays to predict the strength of cell-based flow cytometric (FC) and complement-dependent cytotoxicity (CDC) crossmatches. Eighty-two recipient/donors pairs were analyzed using receiver operating characteristic (ROC) curve analyses to determine the accuracy of donor-specific median fluorescence intensity values (Σ MFI) from single antigen bead assays for predicting strong FC and CDC crossmatches.

Reactive oxygen and reactive nitrogen as signaling molecules for caspase 3 activation in acute cardiac transplant rejection.

Apoptosis is a significant factor in cardiac dysfunction and graft failure in cardiac rejection. In this study, we examined potential signaling molecules responsible for caspase 3 activation in a model of acute cardiac allograft rejection. The roles of reactive oxygen species (ROS) and nitric oxide (NO) were determined in untreated allografts and allograft recipients treated with either cyclosporine (CsA), alpha-phenyl-t-butylnitrone (PBN, a spin-trapping agent), vitamin C (VitC), Mn(III)tetrakis (1-methyl-4-pyridyl)porphyrin); MnTmPyP, a superoxide dismutase (SOD) mimetic), or L-(1-iminoethyl)lysine) (L-NIL), an inhibitor of inducible NO synthase (iNOS) enzyme activity.

The complex role of iNOS in acutely rejecting cardiac transplants.

This review summarizes the evidence for a detrimental role of nitric oxide (NO) derived from inducible NO synthase (iNOS) and/or reactive nitrogen species such as peroxynitrite in acutely rejecting cardiac transplants. In chronic cardiac transplant rejection, iNOS may have an opposing beneficial component. The purpose of this review is primarily to address issues related to acute rejection, which is a recognized risk factor for chronic rejection.

Early mortality rates in older kidney recipients with comorbid risk factors.

Background: There are over 60,000 candidates on the deceased donor kidney wait-list and the percentage of candidates over age 50 years continues to grow each year. National data have not previously been used to evaluate the association of comorbidities with mortality in older patients.

Methods: A multivariate analysis of 30,262 deceased donor primary kidney recipients aged 18-59 years and 8,895 aged >or=60 years evaluated the association of six recipient comorbidities on 90- and 365-day patient mortality rates.

A murine model of invasive aspergillosis: variable benefit of interferon-gamma administration under in vitro and in vivo conditions.

Background: Interferon-gamma modulates host defense in a number of infectious diseases. Previous studies have shown that systemic administration of interferon-gamma (IFN-gamma) can enhance survival in experimental invasive aspergillosis (IA).

Methods: Using a novel model of murine IA that is characterized by primary pulmonary infection, we investigated the role of IFN-gamma in the phagocytosis and killing of Aspergillus fumigatus by murine neutrophils and pulmonary alveolar macrophages in vitro and the impact of systemic and regional administration of IFN-gamma on the course of IA in glucocorticoid-treated mice.

Post-translational modification of manganese superoxide dismutase in acutely rejecting cardiac transplants: role of inducible nitric oxide synthase.

Background: Nitration of a critical tyrosine residue in the active site of manganese superoxide dismutase (MnSOD) can lead to enzyme inactivation. In this study, we examined the effect of inducible nitric oxide synthase (iNOS) on MnSOD expression, activity and nitration in acutely rejecting cardiac transplants.

Methods: Lewis (isograft) or Wistar-Furth (allograft) donor hearts were transplanted into Lewis recipient rats.

Hierarchical change in antioxidant enzyme gene expression and activity in acute cardiac rejection: role of inducible nitric oxide synthase.

Reactive oxygen and nitrogen may mediate inflammation injury, but the status of the antioxidant defense system that might influence this process is unknown. In the present study, we examined the expression profile of the antioxidant enzymes, manganese superoxide dismutase (MnSOD), catalase and glutathione peroxidase (GPX) in acutely rejecting cardiac allografts and the potential role of inducible nitric oxide synthase (iNOS) in modulating antioxidant gene expression and activity. Donor hearts from Lewis (isograft) or Wistar-Furth (allograft) rats were transplanted into Lewis recipient rats.

Protective mechanisms of a metalloporphyrinic peroxynitrite decomposition catalyst, WW85, in rat cardiac transplants.

Nitric oxide (NO) derived from inducible NO synthase has been implicated in cardiac rejection. However, little is known about the role of the reactive nitrogen species peroxynitrite. We examined the protective actions of a peroxynitrite decomposition catalyst, WW85, in an experimental model of acute cardiac rejection.

Treatment with {alpha}-phenyl-N-tert-butylnitrone, a free radical-trapping agent, abrogates inflammatory cytokine gene expression during alloimmune activation in rat cardiac allografts.

Spin-trapping nitrones such as alpha-phenyl-N-tert-butylnitrone (PBN) have traditionally been used to trap and stabilize free radicals for detection by electron paramagnetic resonance (EPR) spectroscopy. Unlike classical antioxidants, these agents have never been evaluated therapeutically in allograft transplantation. In the present study, we examined potential mechanisms of action of treatment with PBN in a rat model of acute cardiac allograft transplantation.

Inhibition of nitrosylation, nitration, lymphocyte proliferation, and gene expression in acute and delayed cardiac allograft rejection by an orally active dithiocarbamate.

Dithiocarbamate derivatives sequester metals such as iron and may have benefits in inflammatory diseases. We examined the actions of a new dithiocarbamate-based oral formulation, NOX-700, on protein modification by nitric oxide (NO), gene expression, and lymphocyte proliferation in a model of acute and delayed cardiac rejection. Chronic treatment with NOX-700 prolonged graft survival.

Variable efficacy of N6-(1-iminoethyl)-L-lysine in acute cardiac transplant rejection.

We examined the efficacy and mechanism of action of N(6)-(1-iminoethyl)-L-lysine (L-NIL), a highly selective inhibitor of inducible nitric oxide (NO) synthase (iNOS), on acute cardiac transplant rejection. L-NIL produced a concentration-dependent attenuation of plasma NO by-products and a decrease in nitrosylation of heme protein without altering protein levels of iNOS. At postoperative day 4, L-NIL did not alter the increased binding activities for transcription factors nuclear factor-kappaB and activator protein-1.

A dithiocarbamate analogue decreases intraislet cell infiltration and the incidence of diabetes mellitus in the genetic diabetes-prone BB rat.

Dithiocarbamates are a class of agents that have interesting biologic properties including the ability to limit the production and/or action of nitric oxide (NO). These agents are also potential immunosuppressant agents. Since immunosuppressant agents have been examined for remission of disease in clinical trials, we wanted to examine whether a dithiocarbamate analogue, NOX-200, might inhibit diabetogenesis in the genetic diabetes-prone BB rat model.

Beta tryptase levels are not elevated in patients undergoing liver transplantation.

Reperfusion syndrome during liver transplantation and anaphylaxis are clinical syndromes that share similarities in physiological responses. The liver and intestine contain a variety of immunologically active cells, including mast cells. The purpose of this study is to investigate the possibility that mast-cell degranulation occurs routinely during transplantation and thereby contributes to hemodynamic instability and coagulopathy.

Mechanisms of the protective action of diethyldithiocarbamate-iron complex on acute cardiac allograft rejection.

In this study, we examined the actions of diethyldithiocarbamate-iron (DETC-Fe) complex in acute graft rejection heterotopically transplanted rat hearts. Chronic treatment with DETC-Fe inhibited the increase in plasma nitric oxide (NO) metabolites and nitrosylation of myocardial heme protein as determined by electron paramagnetic resonance (EPR) spectroscopy. Pulse injection with DETC-Fe normalized NO metabolites.

Non-heme iron protein: a potential target of nitric oxide in acute cardiac allograft rejection.

We examined iron nitrosylation of non-heme protein and enzymatic activity of the Fe-S cluster protein, aconitase, in acute cardiac allograft rejection. Heterotopic transplantation of donor hearts was performed in histocompatibility matched (isografts: Lewis --> Lewis) and mismatched (allografts: Wistar-Furth --> Lewis) rats. On postoperative days (POD) 4-6, Western blot analysis and immunohistochemistry revealed inducible nitric-oxide synthase (iNOS) protein in allografts but not isografts.

Transplant tumor registry: donor related malignancies.

Background: Transmission of donor malignancies has been intermittently reported since the early days of clinical transplantation. The incidence of United States donor related malignancies has not previously been documented.

Methods: All donor related malignancies reported to the Organ Procurement and Transplantation Network/United Network for Organ Sharing from 4/1/94-7/1/01 in a cohort of 34,933 cadaveric donors and 108,062 recipients were investigated by contacting the transplant centers to verify that the reported tumors were of donor origin.

Prolonging organ allograft survival: potential role of nitric oxide scavengers.

A growing number of studies suggest a key role of nitric oxide (NO) derived from the inducible NO synthase (iNOS) isoform as a signalling molecule leading to acute organ transplant rejection. Current theory suggests that NO targets certain tissue proteins for nitrosylation or nitration leading to inhibition of enzyme/protein function and to cell death via apoptosis. Gene expression of iNOS and formation of nitrotyrosine residues have been confirmed in biopsies of rejecting grafts in humans.

A ruthenium (III) polyaminocarboxylate complex, a novel nitric oxide scavenger, enhances graft survival and decreases nitrosylated heme protein in models of acute and delayed cardiac transplant rejection.

Nitric oxide (NO) derived from the up-regulation of inducible NO synthase (iNOS) is believed to play an important role in organ rejection. In experimental models of acute cardiac transplant rejection (i.e.