Translational research : the journal of laboratory and clinical medicine
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The beautiful and complex brain machinery is perfectly synchronized, and our bodies have evolved to protect it against a myriad of potential threats. Shielded physically by the skull and chemically by the blood brain barrier, the brain processes internal and external information so that we can efficiently relate to the world that surrounds us while simultaneously and unconsciously controlling our vital functions. When coupled with the brittle nature of its internal chemical and electric signals, the brain's "armor" render accessing it a challenging and delicate endeavor that has historically limited our understanding of its structural and neurochemical intricacies. In this review, we briefly summarize the advancements made over the past 10 years to decode the brain's neurochemistry and neuropharmacology in situ, at the site of interest in the brain, with special focus on what we consider game-changing emerging technologies (eg, genetically encoded indicators and electrochemical aptamer-based sensors) and the challenges these must overcome before chronic, in situ chemosensing measurements become routine.
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We recently described the persistence of detectable serum proinsulin in a large majority of individuals with longstanding type 1 diabetes (T1D), including individuals with undetectable serum C-peptide. Here, we sought to further explore the mechanistic etiologies of persistent proinsulin secretion in T1D at the level of the islet, using tissues obtained from human donors. Immunostaining for proinsulin and insulin was performed on human pancreatic sections from the Network for Pancreatic Organ Donors with Diabetes (nPOD) collection (n = 24). ⋯ Laser capture microdissection followed by mass spectrometry revealed reductions in the proinsulin processing enzymes prohormone convertase 1/3 (PC1/3) and carboxypeptidase E (CPE) in T1D donors. Twenty-four hour treatment of human islets with inflammatory cytokines reduced mRNA expression of the processing enzymes PC1/3, PC2, and CPE. Taken together, these data provide new mechanistic insight into altered proinsulin processing in long-duration T1D and suggest that reduced β cell prohormone processing is associated with proinflammatory cytokine-induced reductions in proinsulin processing enzyme expression.
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This study sought to evaluate perisplenic artery nerve distribution and the feasibility of splenic artery denervation (SDN). The NEXION radiofrequency catheter was used to perform SDN in healthy and inflammatory arthritis pigs. Splenic artery anatomy, nerve distribution, and splenic norepinephrine (NEPI) levels were evaluated before and after SDN. ⋯ The majority of perisplenic arterial nerves are within close proximity of the lumen and are primarily sympathetic efferent fibers. Nerves in the mid-segment may be the preferred SDN target given their proximity to the artery and paucity of periarterial off-target organs. SDN appears safe and effective at reducing splenic NEPI levels.