Factors shaping the composition of the cutaneous microbiota

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Post-transplantation morphological and functional changes in kidneys from expanded criteria donors

Introduction Despite an increase in the number of cadaver donors and overall organ transplantations, the dramatic increase in the waiting list makes it necessary to reconsider donor criteria. The authors wanted to examine whether differences could exist in the function and/or morphology of transplanted kidneys originated from expanded criteria donors (ECDs) and ideal donors 1 and 5 years after transplantation. Methods Kidney function and histopathologic findings were analyzed and compared 1 and 5 years after transplantation in 97 patients having ECD kidneys and in 178 patients who received ideal donor kidneys (IDK). Results Serum creatinine level was significantly higher (p = 0.001) and estimated glomerular filtration rate was significantly lower (p = 0.003) in patients having ECD kidneys as compared with those with IDK 5 years after transplantation. Morphological changes in the transplanted kidneys, such as tubulitis (p = 0.025) and interstitial inflammation (p = 0.002), were significantly more frequently present in patients with ECD kidneys than in those with IDK 1 year after transplantation. Conclusion Despite an absence of differences in kidney function 1 year after kidney transplantation between patients having ECD and IDK, morphological differences in the transplanted kidneys can be detected between the two groups of patients

Transfer of complex regional pain syndrome to mice via human autoantibodies is mediated by interleukin-1–induced mechanisms

Neuroimmune interactions may contribute to severe pain and regional inflammatory and autonomic signs in complex regional pain syndrome (CRPS), a posttraumatic pain disorder. Here, we investigated peripheral and central immune mechanisms in a translational passive transfer trauma mouse model of CRPS. Small plantar skin–muscle incision was performed in female C57BL/6 mice treated daily with purified serum immunoglobulin G (IgG) from patients with longstanding CRPS or healthy volunteers followed by assessment of paw edema, hyperalgesia, inflammation, and central glial activation. CRPS IgG significantly increased and prolonged swelling and induced stable hyperalgesia of the incised paw compared with IgG from healthy controls. After a short-lasting paw inflammatory response in all groups, CRPS IgG-injected mice displayed sustained, profound microglia and astrocyte activation in the dorsal horn of the spinal cord and pain-related brain regions, indicating central sensitization. Genetic deletion of interleukin-1 (IL-1) using IL-1αβ knockout (KO) mice and perioperative IL-1 receptor type 1 (IL-1R1) blockade with the drug anakinra, but not treatment with the glucocorticoid prednisolone, prevented these changes. Anakinra treatment also reversed the established sensitization phenotype when initiated 8 days after incision. Furthermore, with the generation of an IL-1β floxed(fl/fl) mouse line, we demonstrated that CRPS IgG-induced changes are in part mediated by microglia-derived IL-1β, suggesting that both peripheral and central inflammatory mechanisms contribute to the transferred disease phenotype. These results indicate that persistent CRPS is often contributed to by autoantibodies and highlight a potential therapeutic use for clinically licensed antagonists, such as anakinra, to prevent or treat CRPS via blocking IL-1 actions

Enhancements on multi-exposure LASCA to reveal information of speed distribution

Laser Speckle Contrast Analysis (LASCA) has been proven to be a highly useful tool for the full-field determination of the blood perfusion of a variety of tissues. Some of the major advantages of this technique are its relatively high spatial and temporal resolution as well as its good or excellent accordance to Doppler systems. However, traditionally it is only able to report a single characteristic speed regarding to the actual range of interest. This might be misleading if multiple characteristic speeds are present (e. g. tremor and perfusion in skin) or if several kinds of tissues are mixed (e. g. parenchyma and vessels in brain). Here we present two relatively simple extensions of LASCA for these problems. The application of multiple autocorrelation functions (combined with the usage of multiple exposure times) can help in the separation of multiple characteristic speeds. We also present a useful method for the separation of information those originate from a mixture of different tissues. The latter method can be also implemented to single-exposure systems

Chronic treatment with rofecoxib but not ischemic preconditioning of the myocardium ameliorates early intestinal damage following cardiac ischemia/reperfusion injury in rats

There is some recent evidence that cardiac ischemia/reperfusion (I/R) injury induces intestinal damage within days, which contributes to adverse cardiovascular outcomes after myocardial infarction. However, it is not clear whether remote gut injury has any detectable early signs, and whether different interventions aiming to reduce cardiac damage are also effective at protecting the intestine. Previously, we found that chronic treatment with rofecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2), limited myocardial infarct size to a comparable extent as cardiac ischemic preconditioning (IPC) in rats subjected to 30-min coronary artery occlusion and 120-min reperfusion. In the present study, we aimed to analyse the early intestinal alterations caused by cardiac I/R injury, with or without the above-mentioned infart size-limiting interventions. We found that cardiac I/R injury induced histological changes in the small intestine within 2 h, which were accompanied by elevated tissue level of COX-2 and showed positive correlation with the activity of matrix metalloproteinase-2 (MMP-2), but not of MMP-9 in the plasma. All these changes were prevented by rofecoxib treatment. By contrast, cardiac IPC failed to reduce intestinal injury and plasma MMP-2 activity, although it prevented the transient reduction in jejunal blood flow in response to cardiac I/R. Our results demonstrate for the first time that rapid development of intestinal damage follows cardiac I/R, and that two similarly effective infarct size-limiting interventions, rofecoxib treatment and cardiac IPC, have different impacts on cardiac I/R-induced gut injury. Furthermore, intestinal damage correlates with plasma MMP-2 activity, which may be a biomarker for its early diagnosis