We tested whether the combined nano-formulation, prepared with curcumin (anti-inflammatory and neuroprotective molecule) and embryonic stem cell exosomes (MESC-exocur), restored neurovascular loss following an ischemia reperfusion (IR) injury in mice. IR-injury was created in 8–10 weeks old mice and divided into two groups. Out of two IR-injured groups, one group received intranasal administration of MESC-exocur for 7 days. Similarly, two sham groups were made and one group received MESC-exocur treatment. The study determined MESC-exocur reduced neurological score, infarct volume and edema following IR-injury. As compared to untreated IR group, MESC-exocur treated-IR group showed reduced inflammation and N-methyl-D-aspartate receptor expression. Treatment of MESC-exocur also reduced astrocytic GFAP expression and alleviated the expression of NeuN positive neurons in IR-injured mice. In addition, MESC-exocur treatment restored vascular endothelial tight (claudin-5 and occludin) and adherent (VE-cadherin) junction proteins in IR-injured mice as compared to untreated IR-injured mice. These results suggest that combining the potentials of embryonic stem cell exosomes and curcumin can help neurovascular restoration following ischemia-reperfusion injury in mice.

To examine the cardioprotective role of A 3 adenosine receptors during myocardial ischemia/reperfusion injury, we tested the effect of N 6 -(3-iodobenzyl)adenosine-5′- N -methyluronamide (IB-MECA), a potent and selective A 3 adenosine receptor agonist, in models of myocardial stunning and infarction in chronically instrumented conscious rabbits. In phase I (studies of myocardial stunning), rabbits were subjected to six 4-minute coronary occlusions, each separated by 4-minute reperfusion periods, after which the recovery of systolic wall thickening was measured (ultrasonic crystals). In phase II (studies of myocardial infarction), rabbits were subjected to a 30-minute coronary occlusion followed by 3 days of reperfusion. In both phases, IB-MECA was administered as an intravenous bolus (100 μg/kg) 10 minutes before the first coronary occlusion. This dose of IB-MECA was determined in pilot studies to have no effect on heart rate, arterial blood pressure, or plasma histamine concentration in rabbits. In phase I, IB-MECA markedly improved the recovery of wall thickening after the six occlusion/reperfusion cycles, and this effect was sustained throughout the 5-hour observation period; the total deficit of wall thickening (a measure of the overall severity of myocardial stunning) was reduced by 68% (control, 129±16 arbitrary units, n=7; IB-MECA, 41±6 arbitrary units, n=6; P <.01). The protective effects of IB-MECA against stunning were completely blocked by pretreatment with the nonselective adenosine receptor antagonist 8- p -sulfophenyl theophylline or the specific protein kinase C inhibitor chelerythrine. In phase II, IB-MECA reduced myocardial infarct size by 61%; infarct size (tetrazolium staining) was 41±4% of the risk region in control animals (n=8) and 16±6% in IB-MECA–treated animals (n=8, P <.01). These results demonstrate that in conscious rabbits the A 3 adenosine receptor agonist IB-MECA confers a powerful protection against both reversible (stunning) and irreversible (infarction) injury during acute myocardial ischemia and reperfusion by a protein kinase C–mediated pathway, suggesting that selective activation of A 3 receptors is an effective means of protecting the ischemic myocardium without hemodynamic changes.

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Transplantation continues to push the frontiers of medicine into domains that summon forth troublesome ethical questions. Looming on the frontier today is human facial transplantation. We develop criteria that, we maintain, must be satisfied in order to ethically undertake this as-yet-untried transplant procedure. We draw on the criteria advanced by Dr. Francis Moore in the late 1980s for introducing innovative procedures in transplant surgery. In addition to these we also insist that human face transplantation must meet all the ethical requirements usually applied to health care research. We summarize the achievements of transplant surgery to date, focusing in particular on the safety and efficacy of immunosuppressive medications. We also emphasize the importance of risk/benefit assessments that take into account the physical, aesthetic, psychological, and social dimensions of facial disfiguration, reconstruction, and transplantation. Finally, we maintain that the time has come to move facial transplantation research into the clinical phase.

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