Non‐HLA‐matched 3rd party vascular allograft in renal transplant may lead to sensitization against donor HLA

3rd party donor vessels are often used for vascular reconstruction in organ transplantation. While current practice ensures that 3rd party vessels are blood group matched, HLA matching to the non‐intended recipient is not performed. This practice potentially sensitizes the recipient and may reduce their future chance of renal transplant from a larger pool of donors. We examined our cohort of renal transplant recipients who received non‐HLA‐matched 3rd party vessels for the de‐novo development of donor‐specific HLA antibodies. Our institution's Human Tissue Authority (HTA) blood vessel registers were examined to identify stored donor vessels and their non‐intended recipients. Donor vessel HLA status was cross‐referenced with the recipient HLA status. Between 2004 and 2014, five patients were identified that received 3rd party non‐HLA‐matched vessels for vascular reconstruction during renal transplantation. Three patients (60%) subsequently developed donor‐specific HLA antibodies. These data provide evidence that use of non‐HLA‐matched stored 3rd party vascular grafts may lead to sensitization in the recipient. Where time permits, HLA matching should be performed to avoid this allogeneic response. Laboratories monitoring DSA should be aware of any patient receiving a non‐HLA‐matched 3rd party vascular graft, and recipients may benefit from increased post‐transplant immunological vigilance.     

Analysis of the action of euxanthone, a plant-derived compound that stimulates neurite outgrowth

We have investigated the neurite growth-stimulating properties of euxanthone, a xanthone derivative isolated from the Chinese medicinal plant Polygala caudata. Euxanthone was shown to exert a marked stimulatory action on neurite outgrowth from chick embryo dorsal root ganglia explanted in collagen gels, in the absence of added neurotrophins. It was also shown to promote cell survival in explanted chick embryo ganglia, and to stimulate neurite outgrowth from isolated adult rat primary sensory neurons in vitro. The further finding that euxanthone stimulates neurite outgrowth from explants of chick embryo retina and ventral spinal cord suggests an action on signaling pathways downstream of neuronal receptors for specific neurotrophic factors. Consistent with this, euxanthone did not promote neurite outgrowth from non-transfected PC12 cells, or from PC12 cells transfected with TrkB or TrkC, under conditions in which these cells extended neurites in response to, respectively, the neurotrophins nerve growth factor, brain-derived neurotrophic factor and neurotrophin 3. Western blot analysis of euxanthone-stimulated dorsal root ganglion explants showed that expression of phospho-mitogen-activated protein (MAP) kinase was up-regulated after 1 h of euxanthone-treatment. Inhibition of the MAP kinase pathway using PD98059, a specific inhibitor of MAP kinase kinase, blocked all euxanthone-stimulated neurite outgrowth. However, analysis of phospho-Akt expression indicated that the phosphatidylinositol-3 kinase-Akt pathway, another major signaling pathway engaged by neurotrophins, is not significantly activated by euxanthone. These results suggest that euxanthone promotes neurite outgrowth by selectively activating the MAP kinase pathway.     

Harvey Cushing's Early Operative Treatment of Skull Base Fractures

Objectives To review Dr. Harvey Cushing''s early surgical cases at the Johns Hopkins Hospital, revealing details of his operative approaches to fractures of the skull base. Design Following institutional review board approval and through the courtesy of the Alan Mason Chesney Archives, we reviewed the Johns Hopkins Hospital surgical files. Setting The Johns Hopkins Hospital, 1896 to 1912. Participants A total of 24 patients underwent operative treatment for suspected fractures of the skull base. Main Outcome Measures The main outcome measure was operative approach, postoperative mortality, and condition recorded at the time of discharge. Results Overall, 23 patients underwent operative treatment for suspected skull base fractures. The mechanisms of injury were known for 22 patients and included work-related injuries (41%), falls (23%), vehicle injuries (32%), and other trauma (5%). One patient had no mechanism of injury specified in the file. The outcome at the time of discharge from the hospital was “well” or “improved” in 12 patients (52%). The remaining 11 patients died during their admission. Conclusions Although Cushing''s experience with selected skull base pathology has been previously reported, the breadth of his contributions to operative approaches to the skull base has been neglected.     

Assessment methods for angiogenesis and current approaches for its quantification

Angiogenesis is a physiological process which describes the development of new blood vessels from the existing vessels. It is a common and the most important process in the formation and development of blood vessels, so it is supportive in the healing of wounds and granulation of tissues. The different assays for the evaluation of angiogenesis have been described with distinct advantages and some limitations. In order to develop angiogenic and antiangiogenic techniques, continuous efforts have been resulted to give animal models for more quantitative analysis of angiogenesis. Most of the studies on angiogenic inducers and inhibitors rely on various models, both in vitro, in vivo and in ova, as indicators of efficacy. The angiogenesis assays are very much helpful to test efficacy of both pro- and anti- angiogenic agents. The development of non-invasive procedures for quantification of angiogenesis will facilitate this process significantly. The main objective of this review article is to focus on the novel and existing methods of angiogenesis and their quantification techniques. These findings will be helpful to establish the most convenient methods for the detection, quantification of angiogenesis and to develop a novel, well tolerated and cost effective anti-angiogenic treatment in the near future.KEY WORDS: Angiogenesis, angiogenesis assays, quantification techniques     

Enhanced electrochemical response of a modified glassy carbon electrode by poly(2-vinlypyridine-b-methyl methacrylate) conjugated gold nanoparticles for detection of nicotine

Poly(2-vinylpyridine-b-methylmethacrylate) coated gold nanoparticles [P(2VP-MMA)-AuNPs] were prepared and characterized by UV-Vis, FTIR, AFM, and zetasizer analysis. Investigation of the potential of the synthesized poly(2-vinylpyridine-b-methylmethacrylate) coated gold nanoparticles [P(2VP-MMA)-AuNPs] for detection of nicotine is the main focus of the current study. P(2VP-MMA)-AuNPs were coated on a glassy carbon electrode (GCE) for electrochemical detection of nicotine by cyclic voltammetry. The effect of molar mass of individual P2VP blocks and total molar mass of the block copolymer is evaluated in the context of an enhanced electrochemical response of the modified GCE for its sensing ability of nicotine in both aqueous and organic media. The electrochemical detection of nicotine is significantly enhanced by modification of the GCE with P(2VP-MMA)-AuNPs.

Poly(2-vinylpyridine-b-methylmethacrylate) coated gold nanoparticles [P(2VP-MMA)-AuNPs] are employed for enhancement of electrochemical response of glassy carbon electrode for nicotine.