[Advanced glycation end products and oxidative stress as a basis for metabolic abnormalities in patients with type 1 diabetes after successful simultaneous pancreas-kidney transplantation].

AIM: To compare advanced glycation end-products (AGE, RAGE) and 3-nitrotyrosine (3-HT) in patients with DM 1 after successful simultaneous pancreas-kidney transplantation (SPK) and kidney transplantation alone (KTA). To assess relationship between levels of AGE, RAGE, 3-HT and renal transplant (RT) function, carbohydrate and mineral metabolism. MATERIALS AND METHODS: The study included 58 patients who received kidney transplantation in end-stage renal disease (ESRD). 36 patients received SPK. There were performed routine laboratory, examination of AGE, RAGE, 3-NT, parathyroid hormone (PTH), 25(OH)vitamin D, calcium, phosphorus, FGF23, osteoprotegerin (OPG), and fetuin-A levels. RESULTS: All patients after SPK reached normoglycemia (HbA1c 5.7 [5.3; 6.1] %; C-peptide 3.24 [2.29; 4.40] ng/ml) with the achievement of significant difference vs patients after KTA. Arterial hypertension (AH) was more frequent in recipients of SPK before transplantation than after (p=0.008). AH also persisted in greater number of cases in patients after KTA than after SPK. Patients after SPK had higher AGE (р=0.0003) and lower RAGE (р=0.000003) levels. OPG in patients after SPK was significantly higher (р=0.04). The correlation analysis revealed significant positive correlation between 3-HT and OPG (p0.05; r=0.30), RAGE and eGFR (r=-0.52), HbA1c (r=0.48), duration of AH (r=0.34), AGE with HbA1c (r=0.51). CONCLUSION: The results of the "metabolic memory" markers analysis may indicate their contribution to the persistence of the metabolic consequences of CKD and DM 1 after achievement of normoglycemia and renal function restoration and their possible participation in development of recurrent nephropathy, vascular calcification, and bone disorders.

Applications of particulate oxygen-generating substances (POGS) in the bioartificial pancreas.

Type-1 Diabetes (T1D) is a devastating autoimmune disorder which results in the destruction of beta cells within the pancreas. A promising treatment strategy for T1D is the replacement of the lost beta cell mass through implantation of immune-isolated microencapsulated islets referred to as the bioartificial pancreas. The goal of this approach is to restore blood glucose regulation and prevent the long-term comorbidities of T1D without the need for immunosuppressants. A major requirement in the quest to achieve this goal is to address the oxygen needs of islet cells. Islets are highly metabolically active and require a significant amount of oxygen for normal function. During the process of isolation, microencapsulation, and processing prior to transplantation, the islets' oxygen supply is disrupted, and a large amount of islet cells are therefore lost due to extended hypoxia, thus creating a major barrier to clinical success with this treatment. In this work, we have investigated the oxygen generating compounds, sodium percarbonate (SPO) and calcium peroxide (CPO) as potential supplemental oxygen sources for islets during isolation and encapsulation before and immediately after transplantation. First, SPO particles were used as an oxygen source for islets during isolation. Secondly, silicone films containing SPO were used to provide supplemental oxygen to islets for up to 4 days in culture. Finally, CPO was used as an oxygen source for encapsulated cells by co-encapsulating CPO particles with islets in permselective alginate microspheres. These studies provide an important proof of concept for the utilization of these oxygen generating materials to prevent beta cell death caused by hypoxia.

Islet Cell Transplantation and Alternative Therapies.

Even though type 2 diabetes rates plateaued, type 1 diabetes continues to increase. Pancreas transplantation is a treatment modality for patients who suffer hypoglycemic unawareness or complications from diabetes. Islet cell transplantation success rates have improved with modification and advances in isolation, transplantation, and new immunosuppression regimens. The new cell sources as well as delivery ways are explored and being tested in human trials.

Clinically Significant Drug Interaction Between Clotrimazole and Tacrolimus in Pancreas Transplant Recipients and Associated Risk of Allograft Rejection.

STUDY OBJECTIVE: To examine the clinical significance of clotrimazole troche discontinuation on tacrolimus trough levels and risk of allograft rejection after pancreas transplantation. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENTS: Sixty-five pancreas transplant recipients (simultaneous pancreas-kidney transplants [39 patients], pancreas after kidney transplants [4 patients], and pancreas transplant alone [22 patients]) who were discharged after transplantation receiving a maintenance immunosuppressive regimen of tacrolimus, mycophenolate, and prednisone, and a clotrimazole troche to prevent oral mucosal candidiasis; per protocol, the clotrimazole troche was discontinued at 3 months after transplantation. MEASUREMENTS AND MAIN RESULTS: Patients were followed for 1 year after transplantation. The primary outcome measure was the difference in tacrolimus trough level before and after discontinuation of the clotrimazole troche. The secondary outcome measure was the difference in tacrolimus trough level when patients were stratified by the cohort that had a documented rejection episode 3-12 months after transplantation (rejection group) and the cohort that did not experience a rejection episode (no-rejection group). The incidence of rejection was evaluated in relation to mean tacrolimus trough concentrations above or below a protocol-defined level of significance (6 ng/ml). For the primary outcome, the mean tacrolimus trough level before discontinuation of the clotrimazole troche was significantly higher than the mean trough level after discontinuation (mean ± SD 9.6 ± 3.0 ng/ml vs 7.1 ± 2.6 ng/ml, p = 0.000003). For the secondary outcome, the mean tacrolimus trough level difference before and after clotrimazole troche discontinuation remained significant in both the no-rejection group (9.5 ± 3.0 ng/ml vs 7.4 ± 2.4 ng/ml, p = 0.00007) and rejection group (10.9 ± 3.3 ng/ml vs 4.1 ± 2.5 ng/ml, p = 0.0008). Between groups, the mean tacrolimus serum trough level after clotrimazole troche discontinuation was lower in the rejection group (4.1 ± 2.5 ng/ml) than that in the no-rejection group (7.4 ± 2.4 ng/ml; p = 0.005). The mean tacrolimus trough level difference between before and after discontinuation was greater in the rejection group (6.8 ± 1.5 ng/ml) versus the no-rejection group (2.1 ± 3.8 ng/ml, p = 0.009). Tacrolimus trough levels below 6 ng/ml (19 patients) after clotrimazole troche discontinuation were associated with an increased incidence of rejection episodes within 3-12 months after transplantation (odds ratio 12, 95% confidence interval 1.24-115.91, p = 0.032) versus trough levels of 6 ng/ml or higher (46 patients). CONCLUSION: Clotrimazole troche discontinuation at 3 months after transplantation may cause significant tacrolimus trough level reductions. In addition, when trough levels are below 6 ng/ml, these fluctuations may contribute to the occurrence of allograft rejection.

Pancreas.

Even though pancreas transplant numbers have steadily declined over the past decade, new listings increased in 2014 compared with the previous year, notably for pancreas transplant alone (PTA) and simultaneous pancreas-kidney transplant. The number of new PTAs also increased over the past two years. Whether this is a sustainable trend remains to be seen. Significant events in 2014 included implementation of a new pancreas allocation system and development of a proposed uniform definition of pancreas graft failure. Meanwhile, overall pancreas transplant rates and outcomes continued to improve. Substantial decline in pancreas after kidney transplants remains a serious concern. SRTR has not published pancreas graft failure data in the program-specific reports for the past two years. While this will not change in the near future, the acceptance of a uniform definition of graft failure is a crucial first step toward resuming graft failure reporting. Continued improvements and innovation, both surgical and immunological, will be critical to keep pancreas transplant as a viable option for treatment of insulin-dependent diabetes. As alternative therapies for diabetes such as islet transplant and artificial pancreas are evolving, improved outcomes with minimizations of complications are more important than ever.

Clinical aspects of fungal infections in diabetes.

Diabetes mellitus is one of the main risk factors of fungal infections of oral cavity, lower part of gastrointestinal tract, skin, foot, urogenital system and blood. Mycosis is a serious diagnostic and therapeutic problem and cause of mortality in diabetes. Fungal infections are also an important problem among hemodialysis patients with diabetes or diabetic patients after pancreas or kidney transplantation This work briefly describes the etiology, symptoms, diagnosis and ways of prophylaxis and treatment of mycosis in diabetic population. There is also emphasized the great connection between effective treatment of mycosis and glycemic control.

Endoscopic botulinum toxin injection for the treatment of diabetic gastropathy in pancreas and islet-cell transplant patients.

OBJECTIVES: Gastroparesis is a well-recognized, long-term complication of diabetes. Prokinetic drugs are often not effective, prompting the development of alternative therapies. We report our experience of using one such alternative, endoscopic botulinum toxin injection, to ameliorate diabetic gastropathy in association with pancreas and islet-cell transplant patients. MATERIALS AND METHODS: Three male diabetic patients aged 42 to 55 years had been treated with botulinum toxin in our center. Two patients were both after-simultaneous pancreas-kidney transplant and 1 was awaiting islet-cell transplant after pancreatectomy. Mechanical gastric outlet obstruction was first excluded by radiological and endoscopic studies. Between 100 and 200 IU of toxin were then injected in the prepyloric region using an endoscopic technique. A subjective scoring scale was used to assess symptoms before and after botulinum therapy. RESULTS: Improvement in subjective symptom severity scoring was seen in all patients, with a posttreatment improvement from 55% to 91%. Such improvement was temporary in 2 patients and long-lasting in 1 patient. CONCLUSIONS: The time for improvement of gastric autonomic function after pancreas or islet-cell transplantation remains unclear. Some patients may continue to be symptomatic, leading to increasing morbidity. However, endoscopic botulinum injections may provide short-term relief while waiting for improvement and spare patients the morbidity associated with more-invasive therapies.

Pretreatment of cisplatin in recipients attenuates post-transplantation pancreatitis in murine model.

Pancreas transplantation is the definite treatment for type 1 diabetes that enables the achievement of long-term normoglycemia and insulin independence. However Post-Transplantation Pancreatitis (PTP) due to ischemia reperfusion (IR) injury and preservation is a major complication in pancreas transplantation. Owning the potential anti-inflammatory effect of Cisplatin (Cis) in liver IR injury, we have examined if Cis could attenuate PTP using a murine model. We found that Cis is able to prevent inflammatory response in PTP. Pretreatment of Cis in recipient mice reduce the impairments of the grafts and hyperamylasimea in the recipients. We documented that the protective mechanism of Cis in PTP involves improvement of microcirculation, reduction of the mononuclear cellular infiltration and apoptosis, suppression of inflammatory cytokine-cascade and inhibition of translocation of high-motility group box protein-1 (HMGB-1) from nucleus to cytoplasm. In short, our study demonstrated that pretreatment of Cis in recipients may reduce the onset of PTP in pancreas transplantation.

[End-stage nephropathy in type 1-diabetes mellitus - kidney transplantation alone or combined with islet or pancreas transplantation?]. / Der nierenkranke Patient mit Typ 1-Diabetes mellitus - Nierentransplantation allein oder mit Insel- oder Pankreastransplantation?

Due to the recent changes in reimbursement politics in islet and pancreas transplantation in Switzerland, the question, which patients with type 1-diabetes mellitus get which form of beta-cell replacement, is of utmost importance for referring physicians. As of July 1, 2010 all forms of islet- or pancreas-transplantations are reimbursed by the Swiss health care system. The limited availability of donor organs and the necessity of transplantation of the islets of several pancreata in order to achieve insulin independence has led to a change in paradigms in Switzerland, where insulin independence by multiple islet transplantations is not the key goal in islet transplantation any longer. The primary goal is achieving a good blood glucose control and avoidance of severe hypoglycaemic episodes. This goal can be achieved in 80 - 90 % of all patients. Only if this goal cannot be achieved by a single islet transplantation, a second or third islet transplantation is performed. By adapting this strategy more patients can benefit from this new therapy. Unlike the North American centers, the Swiss centers in Zurich and Geneva concentrated their efforts on islet after kidney and simultaneous islet kidney transplantation. Due to the organ donor shortage in Switzerland, 50 % of kidney transplants are nowadays living-organ donations, therefore this option has to be included in the decision tree of a beta cell replacement. The choice between islet and pancreas transplantation depends on the existence of diabetes complications (because the perioperative risk is considerably higher in pancreas transplantation) and the potential benefit of a pancreas- or islet transplantation. The first question in the decision tree is, therefore, whether the patient with type 1-diabetes and severe renal failure is a potential candidate for simultaneous pancreas-islet transplantation. If the perioperative risk is considered to be too high, or if revascularisation procedures cannot be done before transplantation, the patient qualifies only for islet transplantation. If a living organ donation for the kidney is possible and the patient not yet on dialysis then the patient can be listed for simultaneous islet-kidney or pancreas-kidney-transplantation. If dialysis is imminent or already performed, a living-donor kidney should be transplanted with the option of a later islet- or pancreas after kidney transplantation. If the patient with type 1-diabetes mellitus is able to maintain a reasonable glycemic level, he would be a good candidate for islet transplantation. If the patient is willing to take the additional risk of complications associated with a pancreas transplant, was never able to maintain a good glycated haemoglobin, has an acceptable perioperative risk, and wishes to become insulin-independent, a simultaneous pancreas-kidney transplant would be recommended. If the kidney has already been transplanted previously, a pancreas- after kidney transplantation would be the procedure of choice. An islet or pancreas transplantation alone is reserved for the patient with type 1-diabetes with a good renal function and frequent life-threatening hypoglycemias, which have to be balanced against the risks of a life-long immunosuppression. In this review article the advantages, disadvantages, and current indications for both beta-cell replacement options in Switzerland are discussed in the light of the available evidence with the help of a new flow chart.

Extended-spectrum beta-lactamase-producing bacterial infections in adult solid organ transplant recipients.

BACKGROUND: Limited research is available evaluating infections due to extended-spectrum ß-lactamase (ESBL)-producing organisms in adult recipients of solid organ transplant (SOT). OBJECTIVE: To evaluate clinical response and rate of recurrence of ESBL-producing organisms in 20 SOT recipients. METHODS: In a retrospective case series, records of adult SOT recipients with an admitting diagnosis of infection and a positive culture for an ESBL-producing organism from January 2003 through August 2006 were reviewed. RESULTS: Twenty patients met inclusion criteria. The median time to infection following transplant was 3.5 years (range 1-23 years). Overall, 85% of the patients received inadequate empiric antibiotic therapy, including ciprofloxacin or piperacillin/tazobactam, to manage their infection. Nineteen patients had clinical resolution; however, 12 patients required at least 1 readmission due to infection recurrence. One patient's death occurred during the study period. The median time to readmission for a recurrence was 41 days (18-455 days). All recurrent infections were caused by the same ESBL-producing pathogen and 10 of 12 (83%) infections occurred at the same site as the initial infection. Among patients with recurrent infections, 75% received inadequate empiric therapy upon readmission. All 12 patients with recurrent infections had successful clinical responses to both initial and recurrent infections. CONCLUSIONS: The provision of inadequate empiric therapy for new and recurrent infections due to ESBL-producing pathogens was common in this study population. SOT recipients with a history of infection due to an ESBL-producing organism presenting with a new infection should receive adequate empiric therapy with a carbapenem agent until a definitive diagnosis can be established.

Hyperbaric oxygen in the treatment of a diabetic foot ulcer.

Although simultaneous pancreas and kidney transplant improves most complications of type 1 diabetes, suppression of the immune system increases the risk for infection. The authors report the case of a patient who, despite receiving a simultaneous pancreas and kidney transplant, subsequently developed neuro-ischemic ulcers of his right foot requiring repeated amputations. He then developed an infected ulcer of his remaining right big toe, with significant implications for his mobility. This ulcer proved resistant to multiple courses of antibiotics and care in a specialist foot clinic but resolved completely following a course of hyperbaric oxygen therapy. The role of hyperbaric oxygen in diabetic foot ulcers is not yet fully established but should be considered in resistant cases with vascular insufficiency and a significant infective component.

The clinical impact of islet transplantation.

Islet cell transplantation has recently emerged as one of the most promising therapeutic approaches to improving glycometabolic control in diabetic patients and, in many cases, achieving insulin independence. Unfortunately, many persistent flaws still prevent islet transplantation from becoming the gold standard treatment for type 1 diabetic patients. We review the state of the art of islet transplantation, outcomes, immunosuppression and--most important--the impact on patients' survival and long-term diabetic complications and eventual alternative options. Finally, we review the many problems in the field and the challenges to islet survival after transplantation. The rate of insulin independence 1 year after islet cell transplantation has significantly improved in recent years (60% at 1 year posttransplantation compared with 15% previously). Recent data indicate that restoration of insulin secretion after islet cell transplantation is associated with an improvement in quality of life, with a reduction in hypoglycemic episodes and potentially with a reduction in long-term diabetic complications. Once clinical islet transplantation has been successfully established, this treatment could even be offered to diabetic patients long before the onset of diabetic complications.

Transplantation for the treatment of type 1 diabetes.

Transplantation of pancreatic tissue, as either the intact whole pancreas or isolated pancreatic islets has become a clinical option to be considered in the treatment of patients with type 1 insulin-dependant diabetes mellitus. A successful whole pancreas or islet transplant offers the advantages of attaining normal or near normal blood glucose control and normal hemoglobin A1c levels without the risks of severe hypoglycemia associate with intensive insulin therapy. Both forms of transplants are also effective at eliminating the occurrence of significant hypoglycemic events (even with only partial islet function evident). Whereas whole pancreas transplantation has also been shown to be very effective at maintaining a euglycemic state over a sustained period of time, thus providing an opportunity for a recipient to benefit from improvement of their blood glucose control, it is associated with a significant risk of surgical and post-operative complications. Islet transplantation is attractive as a less invasive alternative to whole pancreas transplant and offers the future promise of immunosuppression-free transplantation through pre-transplant culture. Islet transplantation however, may not always achieve the sustained level of tight glucose control necessary for reducing the risk of secondary diabetic complications and exposes the patient to the adverse effects of immunosuppression. Although recent advances have led to an increased rate of obtaining insulin-independence following islet transplantation, further developments are needed to improve the long-term viability and function of the graft to maintain improved glucose control over time.

The possible study of HuaXi-1 solution for all intra-abdominal organ preservation: a study in rats.

OBJECTIVE: University of Wisconsin (UW) solution continues to be the most commonly used solution for intra-abdominal organs. However, it is expensive. Therefore, we have formulated HuaXi-1 (HX-1) solution. The aim of this research was to assess the effect of HX-1 solution compared to UW, Collins 2, and hypertonic citrate solutions on intra-abdominal organs. METHODS: The effects of HX-1 solution for all intra-abdominal organ preservation were studied in a noncirculated, isolated, perfused rat liver model, in rat pancreas isografts in diabetic rats, and in a kidney autotransplant model. The effects were investigated by measuring hepatic tissue water content, sinusoidal lining cell mortality, Krebs-Henseleits perfusate, aspartate aminotransferase, the number of livers secreting bile during isolated perfusion, blood glucose, glucose tolerance tests, serum insulin of the rat pancreas-transplant recipients, the maximum serum creatinine levels, kidney graft survival rates, and observing the morphological changes in liver, pancreas, and kidneys. RESULTS: HX-1 solution preserved rat liver well for 24 hours as effectively as UW, rat pancreas as well for 48 hours, and dog kidney as well for 72 hours. CONCLUSION: The experimental findings indicated that HX-1 solution was effective to preserve all intra-abdominal organs; it may simplify cold storage of organs for transplantation.

The low-dose (1 microg) adrenocorticotropin stimulation test in kidney and kidney-pancreas transplant patients: a potential guideline for steroid withdrawal.

Chronic steroid treatment is known to impair the hypothalamic-pituitary adrenal axis (HPA) but the need to assess HPA function prior to withdrawal of steroid therapy in post-transplant patients has not been uniformly accepted. We evaluated the status of the HPA axis in 48 kidney or kidney-pancreas transplant patients who were considered for possible discontinuation of glucocorticoid therapy using a recently validated dynamic test of HPA integrity, the low-dose (1 microg) adrenocorticotropin (ACTH) test. HPA suppression was detected in 29 (60%) of the patients, four of which had severe hypoadrenalism prohibitive of steroid withdrawal. Neither the duration of steroid treatment nor 8:00 am serum cortisol was a useful marker of hypoadrenalism. 8:00 am cortisol in subjects with normal HPA reserve and subjects with partial hypoadrenalism overlapped considerably but levels <5 microg/dL were indicative of severe hypoadrenalism. Pre-withdrawal diagnosis of partial hypoadrenalism allowed the identification of subjects requiring no further steroid replacement under regular daily circumstances. However glucocorticoid supplementation was prescribed in the event of stress such as infection, exceptional effort, trauma or surgery. Individuals with partial HPA impairment, but not patients with severe HPA suppression, improved upon retesting 3 months later. Patients exhibiting normal response to 1 mcg ACTH enjoyed an uneventful course following steroid withdrawal. Since hypoadrenalism is extremely common in post-transplant patients, we recommend the use of the low-dose ACTH test as a convenient method to identify patients with various degrees of hypoadrenalism prior to steroid withdrawal.

[Protective effect of shenfu injection against ischemia-reperfusion injury due to pancreas transplantation in rats].

OBJECTIVE: To investigate the protective effect of Shenfu Injection against ischemia-reperfusion (I/R) injury due to pancreas transplantation in rats, and explore its possible mechanism. METHODS: Six normal SD rats with sham operation were taken as the normal control group, 24 steptozozin-induced diabetic SD rats were randomly divided into 4 groups, with 6 in each group. Except I/R group, the rats in the other groups were intravenous injected with Shenfu Injection (SF,10 mg/kg), Hongshen Injection (HS, 9 mg/kg) and Fuzi Injection (FZ 1 mg/kg) respectively at the day and 30 minutes before pancreas transplantation performed in the SF group, HS group and FZ group, respectively. At the same time, rats in the normal control group and in the I/R group were intravenously injected the same volume of normal saline. The blood glucose was detected before and after reperfusion, and 2 hours later after reperfusion, the contents of serum nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha), the concentrations of malondialdehyde (MDA) , superoxide dismutase (SOD) , and myeloperoxidase (MPO) in the transplanted pancreas tissues were detected. The cell apoptosis of the transplanted pancreas tissue was determined by TUNEL, and the bcl-2 and Bax protein expression was determined by Western blot. RESULTS: After reperfusion, the levels of blood glucose and TNF-alpha decreased and the concentration of NO increased in the SF group, HS group and FZ group, compared with those in the I/R group. The activity of SOD, bcl-2 expression and the ratio of bcl-2 and Bax were higher, while the content of MDA, the activity of MPO, apoptotic indexes, and Bax expression were lower in the SF group, HS group and FZ group than those in the I/R group. CONCLUSION: Shenfu Injection can protect L/R injury due to pancreas transplantation in rats, the possible mechanism may be related to promoting activity of SOD, increasing synthesis of endogenous NO, decreasing the excretion of TNF-alpha, alleviating conglutination and aggregation of polymorphonuclear neutrophils (PMNs) in pancreas, as well as up-regulating Bcl-2 gene expression and down-regulating the Bax gene expression.

Protective effect of shenfu injection against ischemia-reperfusion injury due to pancreas transplantation in rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the protective effect of Shenfu Injection against ischemia-reperfusion (I/R) injury due to pancreas transplantation in rats, and explore its possible mechanism.</p><p><b>METHODS</b>Six normal SD rats with sham operation were taken as the normal control group, 24 steptozozin-induced diabetic SD rats were randomly divided into 4 groups, with 6 in each group. Except I/R group, the rats in the other groups were intravenous injected with Shenfu Injection (SF,10 mg/kg), Hongshen Injection (HS, 9 mg/kg) and Fuzi Injection (FZ 1 mg/kg) respectively at the day and 30 minutes before pancreas transplantation performed in the SF group, HS group and FZ group, respectively. At the same time, rats in the normal control group and in the I/R group were intravenously injected the same volume of normal saline. The blood glucose was detected before and after reperfusion, and 2 hours later after reperfusion, the contents of serum nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha), the concentrations of malondialdehyde (MDA) , superoxide dismutase (SOD) , and myeloperoxidase (MPO) in the transplanted pancreas tissues were detected. The cell apoptosis of the transplanted pancreas tissue was determined by TUNEL, and the bcl-2 and Bax protein expression was determined by Western blot.</p><p><b>RESULTS</b>After reperfusion, the levels of blood glucose and TNF-alpha decreased and the concentration of NO increased in the SF group, HS group and FZ group, compared with those in the I/R group. The activity of SOD, bcl-2 expression and the ratio of bcl-2 and Bax were higher, while the content of MDA, the activity of MPO, apoptotic indexes, and Bax expression were lower in the SF group, HS group and FZ group than those in the I/R group.</p><p><b>CONCLUSION</b>Shenfu Injection can protect L/R injury due to pancreas transplantation in rats, the possible mechanism may be related to promoting activity of SOD, increasing synthesis of endogenous NO, decreasing the excretion of TNF-alpha, alleviating conglutination and aggregation of polymorphonuclear neutrophils (PMNs) in pancreas, as well as up-regulating Bcl-2 gene expression and down-regulating the Bax gene expression.</p>