Background
The instant blood-mediated inflammatory response (IBMIR) has been shown as a major factor that causes damage to transplanted islets. Withaferin A (WA), an inhibitor of nuclear factor κB (NFκB), was shown to suppress the inflammatory response in islets and improve syngeneic islet graft survival in mice. We investigated how treating islets with NFκB inhibitors affected IBMIR using an in vitro human autologous blood islet model.
Methods
Human islets were pretreated with or without NFκB inhibitors WA or CAY10512 before mixing autologous blood in a miniaturized in vitro tube model. Plasma samples were collected at multiple time points and used for the measurement of C-peptide, proinsulin, thrombin-antithrombin (TAT) complex, and a panel of proinflammatory cytokines. Infiltration of neutrophils into islets was analyzed using immunohistochemistry.
Results
Rapid release of C-peptide and proinsulin was observed 3 hours after mixing islets and blood in the control group, but not in the NFκB inhibitor–treated groups, whereas TAT levels were elevated in all three groups with a peak at 6 hours. Significant elevation of proinflammatory cytokines was observed in the control group after 3 hours, but not in the treatment groups. Significant inhibition of neutrophil infiltration was also observed in the WA group compared with the control (P <0.001) and CAY10512 (P <0.001) groups.
Conclusions
A miniaturized in vitro tube model can be useful in investigating IBMIR. The presence of NFκB inhibitor could alleviate IBMIR, thus improving the survival of transplanted islets. Protection of islets in the peritransplant phase may improve long-term graft outcomes.
Orbital compartment syndrome (OCS) is a rare, vision‐threatening diagnosis that requires rapid identification and immediate treatment for preservation of vision. Because of the time‐sensitive nature of this condition, the emergency physician plays a critical role in the diagnosis and management of OCS, which is often caused by traumatic retrobulbar hemorrhage. In this review, we outline pearls and pitfalls for the identification and treatment of OCS, highlighting lateral canthotomy and inferior cantholysis (LCIC), a crucial skill for the emergency physician. We recommend adequate preparation for the diagnosis and procedure, early consultation to ophthalmology, clear and thorough documentation of the physical examination, avoidance of iatrogenic injury during LCIC, and complete division of the inferior canthal tendon. Emergency physicians should avoid failing to make the diagnosis of OCS, delaying definitive surgical treatment, overrelying on imaging, failing to decrease intraocular pressure, and failing to exclude globe rupture. The emergency physician should be appropriately trained to identify signs and symptoms of OCS and perform LCIC in a timely manner.
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