Dexmedetomidine attenuates isoflurane-induced injury in the developing brain, providing neurocognitive protection. Isoflurane-induced injury in vitro appears to be independent of activation of the gamma-amino-butyric-acid type A receptor. If isoflurane-induced neuroapoptosis proves to be a clinical problem, administration of dexmedetomidine may be an important adjunct to prevent isoflurane-induced neurotoxicity.

IntroductionAcute kidney injury following surgery incurs significant mortality with no proven preventative therapy. We investigated whether the α2 adrenoceptor agonist dexmedetomidine (Dex) provides protection against ischemia-reperfusion induced kidney injury in vitro and in vivo.MethodsIn vitro, a stabilised cell line of human kidney proximal tubular cells (HK2) was exposed to culture medium deprived of oxygen and glucose. Dex decreased HK2 cell death in a dose-dependent manner, an effect attenuated by the α2 adrenoceptor antagonist atipamezole, and likely transduced by phosphatidylinositol 3-kinase (PI3K-Akt) signaling. In vivo C57BL/6J mice received Dex (25 μg/kg, intraperitoneal (i.p.)) 30 minutes before or after either bilateral renal pedicle clamping for 25 minutes or right renal pedicle clamping for 40 minutes and left nephrectomy.ResultsPre- or post-treatment with Dex provided cytoprotection, improved tubular architecture and function following renal ischemia. Consistent with this cytoprotection, dexmedetomidine reduced plasma high-mobility group protein B1 (HMGB-1) elevation when given prior to or after kidney ischemia-reperfusion; pretreatment also decreased toll-like receptor 4 (TLR4) expression in tubular cells. Dex treatment provided long-term functional renoprotection, and even increased survival following nephrectomy.ConclusionsOur data suggest that Dex likely activates cell survival signal pAKT via α2 adrenoceptors to reduce cell death and HMGB1 release and subsequently inhibits TLR4 signaling to provide reno-protection.

Dexmedetomidine prevents cortical apoptosis in vitro and in vivo. However, using higher doses of dexmedetomidine does not further increase protection against isoflurane injury in the cortex than previously observed.

Summary The lack of suitable kidney donor organs has led to rising numbers of patients with end stage renal disease waiting for kidney transplantation. Despite decades of clinical experience and research, no evaluation process that can reliably predict the outcome of an organ has yet been established. This review is an overview of current methods and emerging techniques in the field of donor kidney evaluation prior to transplantation. Established techniques like histological evaluation, clinical scores, and machine perfusion systems offer relatively reliable predictions of delayed graft function but are unable to consistently predict graft survival. Emerging techniques including molecular biomarkers, new imaging technologies, and normothermic machine perfusion offer innovative approaches toward a more global evaluation of an organ with better outcome prediction and possibly even identification of targets for therapeutic interventions prior to transplantation. These techniques should be studied in randomized controlled trials to determine whether they can be safely used in routine clinical practice to ultimately reduce the discard rate and improve graft outcomes.

The microbiological safety of islet preparations is paramount. Preservation medium contamination is frequent, and its impact on islet yield and function remains unclear. Microbiological samples collected during islet isolations from 2006 to 2016 were analyzed and correlated to isolation and allo- and autotransplantation outcomes. Microbial contamination of preservation medium was found in 64.4% of processed donor pancreases (291/452). We identified 464 microorganisms including Staphylococcus (253/464, 54.5%), Streptococcus (31/464, 6.7%), and Candida species (25/464, 5.4%). Microbial contamination was associated with longer warm and cold ischemia times and lower numbers of postpurification islet equivalents, purity, transplant rate, and stimulation index (all P < 0.05). Six percent of the preparations accepted for transplantation showed microbial contamination after isolation (12/200); 9 of 12 were Candida species. Six patients were transplanted with a sample with late microbial growth discovered after the infusion. Insulin independence rate was not affected. This risk of transplanting a contaminated islets preparation was reduced by half following the implementation of an additional sampling after 24 h of islet culture. Pancreas preservation fluid microbial contamination is associated with lower transplant rate and poorer in vitro function, but not with changes in graft survival. Culture medium testing 1 day after isolation reduces the risk of incidental transplantation with contaminated islets.

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Robot-assisted donor nephrectomy (RDN) is increasingly used due to its advantages such as its precision and reduced learning curve when compared to laparoscopic techniques. Concerns remain among surgeons regarding possible longer warm ischemia time. This study aimed to compare patients undergoing robotic living donor nephrectomy to the more frequently used hand-assisted laparoscopic nephrectomy (HLDN) technique, focusing on warm ischemia time, total operative time, learning curve, hospital length of stay, donor renal function and post-operative complications. Retrospective study comparing RDN to HLDN in a collaborative transplant network. 176 patients were included, 72 in RDN and 104 in HLDN. Left-sided nephrectomy was favored in RDN (82% vs 52%, p < 0.01). Operative time was longer in RDN (287 vs 160 min; p < 0.01), while warm ischemia time was similar (221 vs 213 secs, p = 0.446). The hospital stay was shorter in RDN (3.9 vs 5.7 days, p < 0.01).Concerning renal function, a slightpersistent increase of 7% of the creatinine ratio was observed in the RDN compared to the HLDN group (1.56 vs 1.44 at 1-month checkup, p < 0.01). The results show that RDN appears safe and efficient in comparison to the gold-standard HLDN technique. Warm ischemia time was similar for both techniques, whereas RDN operative time was longer. Patients undergoing RDN had a shorter hospital stay, this being possibly mitigated by differences in center release criteria. Donor renal function needs to be assessed on a longer-term basis for both techniques.

ReviewXenon, a noble gas discovered more than a century ago, has been known to exhibit anesthetic properties since 1946. Its effects are comparable to the commonly used anesthetic gas, nitrous oxide, and have been well defined (Table 1). Recently, its notable safety and efficacy as an inhalational anesthetic have been studied in various clinical settings [1,2]. However, high manufacturing costs owing to its rarity in the atmosphere remain the limiting factor in its widespread clinical application.As an antagonist of the NMDA subtype of the glutamate receptor [3], xenon has been extensively investigated for its molecular action in neuroprotection against acute neuronal injury. In this review, we aim to briefly describe the NMDA receptor-related mechanisms of ischemic brain injury and focus chiefly on the research progress into xenon's neuroprotective effects and paradigms. NMDA receptor & glutamate excitotoxicityGlutamate is a predominant excitatory neurotransmitter in the mammalian CNS [4]. When intensely activated, it can be toxic to neurons in a range of acute CNS injury conditions [5], including stroke [6], hypoglycemia [7], trauma [8] and status epilepticus [9]. Excess glutamate is also implicated in neurodegenerative conditions [10] with involvement of the NMDA subtype [11,12].Neuronal function and survival relies on a constant supply of oxygen and glucose to produce ATP through glycolysis and mitochondrial respiration. In ischemia and hypoglycemia, energy deficiency results in the dysfunction of the presynaptic neurotransmitter release and leads to a net increase in extracellular glutamate, causing neurotoxicity [13]. Excess glutamate activates its postsynaptic receptors, namely NMDA, a-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and kainate (KA). The activation of AMPA receptors depolarizes the cell and simultaneously unblocks the NMDA channels (by the removal of the Mg 2+ block), thus permitting Ca 2+ entry. Depolarization opens voltageactivated calcium channels, allowing an influx of Ca 2+ ions, as well as H 2 O molecules, down the osmotic gradient into the cell [14][15][16], subjecting the cells to cytotoxicity.The endoplasmic reticulum and mitochondria act as vast storage and regulators for Ca 2+ ions. Beyond a critical point, calcium overload disrupts mitochondrial function. It promotes intracellular enzyme activation systems including lipases, proteases and endonucleases, which cause an overwhelming production of free oxygen radicals, synthesis of nitric oxide [17], mitogen-activated protein kinase (MAPK) [18] and related toxic reaction products, leading to acute neuronal death [11,[19][20][21]. The inner mitochondrial membrane is also disrupted and causes the oxidation of the proteins involved in ATP production [22], reducing energy available for membrane pumps and resulting in apoptosis.Apoptosis is often associated with excitotoxicity, although the link is not well established. A multistep mechanism regulates apoptosis [23], involving the presence of at least two distinct checkpoints -on...