Effect of PERLA®, a new cold-storage solution, on oxidative stress injury and early graft function in rat kidney transplantation model.

BACKGROUND: The composition of organ preservation solutions is crucial for maintaining graft integrity and early graft function after transplantation. The aim of this study is to compare new organ preservation solution PERLA® with the gold standard preservation solution University of Wisconsin (UW) regarding oxidative stress and early graft injury. METHODS: In order to assess oxidative stress after cold storage, kidney grafts have been preserved for 18 h at 4° C in either UW solution or PERLA® solution and then assessed for oxidative stress injury (protocol 1). To assess kidney injuries and oxidative stress after reperfusion, rat kidneys were harvested, stored in cold UW or in PERLA® solutions for 18 h at 4 °C and then transplanted heterotopically for 6 h (protocol 2). PERLA® is a high Na+/low K+ solution including PEG-35 (1 g/L), trimetazidine (1 µM), carvedilol (10 µM) and tacrolimus (5 µM). RESULTS: Our results showed that preservation of kidneys in PERLA® solution significantly attenuates oxidative stress parameters after cold storage and reperfusion. We found a significant decrease in oxidative damage indicators (MDA, CD and CP) and a significant increase in antioxidant indicators (GPx, GSH, CAT, SOD and PSH). Moreover, PERLA® solution decreased kidney injury after reperfusion (creatinine, LDH and uric acid). CONCLUSION: PERLA® solution was more effective than UW storage solution in preserving rat's kidney grafts.

Supplemental hydrogen sulfide in models of renal transplantation after cardiac death.

BACKGROUND: The increasing use of kidneys from donations after cardiac death (DCD) for renal transplantation is hindered by negative outcomes owing to organ injury after prolonged warm and cold ischemia-reperfusion. Recently, hydrogen sulfide (H2S) has shown cytoprotective effects against ischemia-reperfusion injury; however, its effectiveness in the context of DCD renal transplantation is unknown. METHODS: We tested a novel 30-day in vivo syngeneic murine model of DCD renal transplantation, in which the donor kidney was clamped for 30 minutes and stored for 18 hours in cold University of Wisconsin (UW) solution or UW with 150 µM sodium hydrogen sulfide (UW + NaHS) before transplantation. We also tested a 7-day in vivo porcine model of DCD renal autotransplantation, in which the left kidney was clamped for 60 minutes and preserved for 24 hours using hypothermic perfusion with UW or UW + 150 µM NaHS before autotransplantation. We collected blood and urine samples periodically, and collected kidney samples at the end point for histopathology and quantitative reverse transcription polymerase chain reaction. RESULTS: Rats that received H2S-treated kidneys showed significantly higher survival, faster recovery of graft function and significantly lower acute tubular necrosis than controls. Pig kidneys perfused with UW + NaHS showed significantly higher renal blood flow and lower renal resistance than control kidneys after 24 hours of perfusion. After autotransplantation, pigs that received H2S-treated kidneys showed significantly lower serum creatinine on days 1 and 7 after transplantation. Rat and pig kidneys treated with H2S also showed more protective gene expression profiles than controls. CONCLUSION: Our findings support the potential use of H2S-supplemented UW solution during cold storage as a novel and practical means to improve DCD graft survival and function.

Additives to preservation solutions.

As the impact of ischemia reperfusion injury on graft outcome is now well defined, efforts are made towards decreasing these lesions, typically through the improvement of preservation techniques. The use of pharmacological supplements which could be compatible with any preservation solution used by the transplant center and target specific pathways of IR is an interesting strategy to improve graft quality. However, the extensive number of studies showing the benefits a molecule in an animal model of IR without thorough mechanistic determination of the effects of this agent make it difficult to opt for specific pharmaceutical intervention. Herein we expose studies which demonstrate the benefits of several molecules relying on a thorough mechanical analysis of the events occurring during preservation, both at the cellular and the systemic levels. We believe this approach is the most appropriate to truly understand the potential benefits of a molecule and particularly to design a comprehensive pharmaceutical regiment, with several agents acting synergistically against IR, to improve organ preservation and graft outcome.

Polyethylene glycols and organ protection against I/R injury.

During the organ transplantation process, conservation solutions must address responses to the physiologic organ preservation and prevent ischemia-reperfusion injuries. The use of colloids seems beneficial especially for long ischemia time compared to the impermeant molecules used for short time. The colloids family includes molecules as hydroxyethyl starch (HES), albumin, dextran or polyethylene glycol (PEG). In this review, the authors describe the rational for PEG use, its potential immunomodulatory effect and the main results of its experimental and clinical use.

Dental trauma management awareness among primary school teachers in the Emirate of Ajman, United Arab Emirates.

AIM: To assess, by means of self-administered structured questionnaire, the level of knowledge of primary schools teachers in Ajman with regards to the immediate emergency management of dental trauma. MATERIALS AND METHODS: The questionnaire was sent to teachers in randomly selected primary schools in Ajman. A total of 161 teachers responded (response rate 84.4%). The questionnaire surveyed teachers' background, knowledge and management of tooth fracture, avulsion, and also investigated teachers' attitudes and self-assessed knowledge. RESULTS: Ninety-one percent of the teachers were females, 51.6% in their thirties and 61.5% had university qualification. Fifty teachers had received formal first aid training, and only thirteen of them recalled that they had received training on the management of dental trauma. Concerning the management of tooth fracture, 138 respondents (85.8%) gave the appropriate management for fractured tooth. One hundred twenty-one (75%) of the respondents indicated that is very urgent to seek professional assistance if a permanent tooth is avulsed, but they had little knowledge on the correct media for transporting the avulsed tooth. Most teaches were unsatisfied with their level of knowledge for dental trauma and the majority were interested in having further education on the topic. CONCLUSION: The findings revealed that the level of knowledge of management of dental trauma (especially tooth avulsion) among school teachers in Ajman is inadequate, and education campaigns are necessary to improve their emergency management of dental injuries.

Pharmacological Benefits and Risk of Using Hormones in Organ Perfusion and Preservation Solutions in the Aspect of Minimizing Hepatic Ischemia-Reperfusion Injury during Storage.

For several years, research has been carried out on the effectiveness of solutions for perfusion and preservation of organs, including the liver. There is a search for an optimal pharmacological composition of these solutions, allowing to preserve or improve vital functions of the organ for as long as possible until it is transplanted into a recipient. Hormones due to their properties, often resulting from their pleiotropic effects, may be a valuable component for optimizing the composition of liver perfusion and preservation solutions. The paper presents the current state of knowledge on liver perfusion and preservation solutions modified with hormones. It also shows the characteristics of the hormones evaluated, taking into account their physiological functions in the body.

The use of oxygenated perfluorocarbonic emulsion for initial in situ kidney perfusion.

Protection of grafts from ischemia-reperfusion injury (IRI) remains an important problem, especially in uncontrolled donors. This study was performed to define the effect of oxygenated perfluorocarbonic emulsion for initial in situ conservation. One hundred and seventeen kidney grafts were procured from 2003 until 2006 from sixty one DCDs of Maastricht II and IV category. Control group donors (HTK group, n = 31) were operated using the traditional rapid laparotomy. The study group donors (Perftoran group, n = 30) had femoral access obtained in the ICU with initial perfusion by perfluorocarbonic PFG emulsion. The recipients were divided according to the type of the initial perfusion of the kidneys into a control group (n = 59) whose kidneys were initially perfused using HTK solution, and a study group (n = 58), who received kidneys preserved with initial perfusion in situ using oxygenated Perftoran. The rate of delayed graft function was significantly (up to 30%) higher among the control group. In the study group, the rate of immediate function was twice as high as that in the control group. By postoperative day 21, the level of serum creatinine in the study group decreased twice that of the control group. Initial perfusion with oxygenated perfluorocarbonic emulsion in situ may minimize a IRI of DCD kidneys.

Celsior versus Wisconsin solution in pancreas transplantation.

Celsior solution (CS), which has recently become available, that might theoretically offer a new means for improving graft preservation quality. The present prospective, randomized study was designed to evaluate the efficacy of CS compared with University of Wisconsin (UW) for pancreas allografts. Between January 2001 and January 2007, 88 patients underwent pancreatic transplantation, including the last 30 consecutive simultaneous pancreas kidney patients who were randomly assigned to either CS or UW. There was no case of graft thrombosis in either group. There were 2 cases of pancreatitis in the UW group compared with 1 in the CS group. No case of primary nonfunction occurred in either group. There were 2 cases of early duodenal stump fistulae in the CS group that required transplantectomy, whereas this complication was not observed in the UW group. Relaparotomy in the UW group was required in 3 cases due to infection and treated by close drainage that which, progressed to fatal sepsis in 1 patient. In the UW group with 6 months of follow-up, there were 12 patients insulin free. In the CS group, 6 patients underwent relaparotomy, 3 for transplantectomy and the others for intra-abdominal infection, which was fatal in 2 cases. In the CS group with 6 months of follow-up, there were 10 patients insulin free. Two patients died with functioning grafts. These results provided indirect evidence that CS solution is at least as safe as UW to mitigate postreperfusion graft edema and pancreatitis, as well as graft thrombosis.

Tips for optimizing organ preservation solutions.

Organ injury during ischemia is one of the clinical problems of today's transplantation. It occurs during warm ischemia time (WIT) when the blood flow is cut off and during cold ischemia when a graft is chilled in situ until the circulation is restored to the recipient organism. Fast cooling of the organ slows down metabolism and activates intracellular enzymes, which minimizes the effects of warm ischemia. Unfortunately, hypothermia also results in inhibition of ATP synthesis, cell swelling and intracellular acidity. That is why research is continually being conducted to develop new fluids for rinsing and storing organs, as well as to optimize the composition of those that are already in use, which will allow for longer and more effective graft storage and restoration of their optimal functions after transplantation. This article provides current information on rinsing and storage fluids available on the global market. It also discusses tips for the fluid modifications with hormones and micronutrients.

Preservation solutions for solid organ transplantation.

Solid organ transplantation was one of the greatest medical advances of the 20th century. Current preservation technology falls short of maintaining organs ex vivo in perpetuity. This review examines the biochemical basis of organ degradation in response to ischaemia, preservation solution composition and potential future organ preservation technology.

Past and future approaches to ischemia-reperfusion lesion associated with liver transplantation.

Ischemia-reperfusion (I/R) injury associated with liver transplantation remains a serious complication in clinical practice, in spite of several attempts to solve the problem. The present review focuses on the complexity of I/R injury, summarizing conflicting results obtained from the literature about the mechanisms responsible for it. We also review the therapeutic strategies designed in past years to reduce I/R injury, attempting to explain why most of them have not been applied clinically. These strategies include improvements in pharmacological treatments, modifications of University of Wisconsin (UW) preservation solution based on a variety of additives, and gene therapy. Finally, we will consider new potential protective strategies using trimetazidine, 5-amino-4-imidazole carboxamide riboside (AICAR), melatonin, modulators of the renin-angiotensin system (RAS) and the phosphatidylinositol-3-OH kinase (PI3K)-Akt and the p42/p44 extracellular signal-regulated kinases (Erk 1/2) pathway. These strategies have shown promising results for I/R injury but have not been tested in experimental liver transplantation to date. Moreover, we will review ischemic preconditioning, taking into account the recent clinical studies that suggest that this surgical strategy could be appropriate for liver transplantation.

Potential benefits of melatonin in organ transplantation: a review.

Organ transplantation is a useful therapeutic tool for patients with end-stage organ failure; however, graft rejection is a major obstacle in terms of a successful treatment. Rejection is usually a consequence of a complex immunological and nonimmunological antigen-independent cascade of events, including free radical-mediated ischemia-reperfusion injury (IRI). To reduce the frequency of this outcome, continuing improvements in the efficacy of antirejection drugs are a top priority to enhance the long-term survival of transplant recipients. Melatonin (N-acetyl-5-methoxytryptamine) is a powerful antioxidant and ant-inflammatory agent synthesized from the essential amino acid l-tryptophan; it is produced by the pineal gland as well as by many other organs including ovary, testes, bone marrow, gut, placenta, and liver. Melatonin has proven to be a potentially useful therapeutic tool in the reduction of graft rejection. Its benefits are based on its direct actions as a free radical scavenger as well as its indirect antioxidative actions in the stimulation of the cellular antioxidant defense system. Moreover, it has significant anti-inflammatory activity. Melatonin has been found to improve the beneficial effects of preservation fluids when they are enriched with the indoleamine. This article reviews the experimental evidence that melatonin is useful in reducing graft failure, especially in cardiac, bone, otolaryngology, ovarian, testicular, lung, pancreas, kidney, and liver transplantation.

Successful islet transplantation from a single pancreas harvested from a young, low-BMI, non-heart-beating cadaver.

BACKGROUND: Young donors, donors with low body mass index (BMI), and non-heart-beating (NHB) donors are considered nonideal for islet transplantation. In this report, we successfully used a pancreas from a young, low-BMI, NHB donor for islet transplantation. METHODS: The donor was a 15-year-old adolescent boy whose cause of death was rupture of a primary brain tumor. According to Japanese regulations, his pancreas was procured after cardiac arrest. Warm ischemic time was 3 minutes and cold ischemic time was 300 minutes. The pancreas was digested by the automated method of Ricordi, followed by purification using continuous Euro-Ficoll gradients on a Cobe 2991 device. The recipient was a 35-year-old woman with unstable type 1 diabetes mellitus. Her pretransplant C-peptide level was null. She suffered frequent hypoglycemic unawareness. Her pretransplant M value, which is a good marker for glucose instability, was 125. Islet yield was 252,816 IEQ. There were no signs of contamination. Viability of islets assessed by FDA/PI staining was 83%. Stimulation index was 2.7. RESULTS: The patient received 5160 IEQ/kg of islets via the portal vein under local anesthesia. There were no transplant-related complications. Although she required minimal exogenous insulin, her C-peptide level increased to 0.7 ng/mL at postoperative day (POD) 14. Her M value at POD 15 to 19 decreased dramatically to 23.6, indicating good glycemic control. At 3 months posttransplant, episodes of hypoglycemia disappeared. CONCLUSIONS: Although an additional transplant is mandatory to wean patients from insulin, this case shows the possibility of using marginal donors, such as a young, low-BMI, NHB donor, for pancreas islet transplantation.

Major upper limb replantation.

Major amputations remain a challenge to the replantation surgeon. Proper patient selection, good surgical skills, and cooperation among the patient, surgeon, and rehabilitation team help achieve a better outcome.

Brazilian primary school teachers' knowledge about immediate management of dental trauma.

OBJECTIVE: To assess the level of knowledge of primary school teachers in the public school network of Northeastern Brazil with respect to management of dental trauma and its relationship with prognosis. METHODS: A questionnaire was applied to 195 school teachers of public schools in Northeastern Brazil. The questionnaire comprised 12 objective questions about dental trauma and methods for its prevention and management. Data were submitted to chi-square test and Poisson regression test (P > 0.05). RESULTS: Out of the 141 teachers who responded the questionnaires, the majority were women (70.2%) and most of them had experienced previous dental accidents involving a child (53.2%). The majority (84.4%) had incomplete college education and few were given some training on how to deal with emergency situations during their undergraduate course (13.5%) or after it (38.3%). Their level of knowledge about dental trauma and emergency protocols showed that unsatisfactory knowledge level was associated with the male sex: 46% higher for men in comparison to women (P = 0.025). CONCLUSIONS: Approximately half of teachers evaluated had unsatisfactory knowledge about dental trauma and emergency protocols, with female teachers showing more knowledge than men.

How Institut Georges Lopez preservation solution protects nonsteatotic and steatotic livers against ischemia-reperfusion injury.

The Institut Georges Lopez preservation solution (IGL-1) is a serum-free organ preservative that has been shown to protect steatotic livers against hepatic ischemia-reperfusion injury. Although several hypotheses have been proposed to explain the graft protection mechanisms induced by IGL-1 solution, they have not been fully investigated. This review assessed possible IGL-1 mechanisms responsible for the increased liver tolerance of ischemia-reperfusion injury with special emphasis on vasodilatator mediators such as nitric oxide, on oxidative stress prevention, on protection against mitochondrial damage, and finally on induction of cytoprotective factors.