The role of corticosterone in human hypothalamic– pituitary–adrenal axis feedback

Objective  In humans, the glucocorticoid corticosterone circulates in blood at 10–20-fold lower levels than cortisol, but is found in higher relative amounts in postmortem brain samples. Access of cortisol and corticosterone to the central nervous system may not be equal. Additionally, the relative affinities for the glucocorticoid and mineralocorticoid receptors differ, such that corticosterone may play a significant role in human brain function. Design  We measured cortisol and corticosterone levels in paired plasma and cerebrospinal fluid (CSF) samples. To test the relative potency of cortisol vs. corticosterone on hypothalamic–pituitary–adrenal (HPA) feedback, subjects underwent a three-phase, single-blind, randomized study assessing the postmetyrapone ACTH response over 3 h to an intravenous bolus of vehicle, cortisol or corticosterone (0·15 mg/kg and 0·04 mg/kg). Participants  Outpatients undergoing diagnostic lumbar puncture who were subsequently deemed to be free of disease. Feedback was tested in healthy male volunteers. Measurements  Plasma and CSF corticosterone to cortisol ratio was calculated and the ACTH response over time after the bolus glucocorticoid measured. Results  Plasma corticosterone : cortisol was 0·069 ± 0·007; CSF corticosterone : cortisol was 0·387 ± 0·050 ( P <  0·001). Cortisol and corticosterone (0·15 mg/kg) suppressed ACTH vs. vehicle ( P =  0·002); there was no difference between corticosterone and cortisol. The 0·04 mg/kg dose had no effect on ACTH despite supraphysiological plasma corticosterone levels. Conclusions  Corticosterone contributes almost 40% of total active glucocorticoids (cortisol and corticosterone) in the CSF. Significant effects on HPA axis suppression were only seen with supraphysiological levels of corticosterone, suggesting that corticosterone is not important in this model of nonstress-induced ACTH hypersecretion, in which the effect of cortisol predominates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72329/1/j.1365-2265.2006.02540.x.pd

Face Value: The Rhetoric of Facial Disfigurement in American Film and Popular Culture, 1917-27

This is the author accepted manuscript. The final version is available from Taylor & Francis via the DOI in this record.The return of facially disfigured men from the trenches of World War One occasioned a muted public reaction in the US. However, this article will show that burgeoning discourses concerning plastic surgery in the US also generated a significant reaction in the popular press, and that these were reflected, too, in several feature films dealing with facial surgery on disfigured veterans. Though several of these films depicted miraculous transformations occasioned by the surgeons, Robert Florey’s 1927 film, Face Value, focused on an American veteran with facial scarring that could not be repaired. The article will argue that this film drew strongly upon the increasingly prominent public presence of the gueules cassées in the US during 1926 and 1927. Depicting gueules cassées and their facial injuries prominently in several scenes, the film brought to attention difficult questions concerning the futures of such men, which the US media had hitherto rarely addressed

Dual regeneration of muscle and nerve by intravenous administration of human amniotic fluid-derived mesenchymal stem cells regulated by stromal cell-derived factor-1 alpha in a sciatic nerve injury model

Object. Human amniotic fluid-derived mesenchymal stem cells (AFMSCs) have been shown to promote peripheral nerve regeneration. The expression of stromal cell-derived factor-1 alpha (SDF-1 alpha) in the injured nerve exerts a trophic effect by recruiting progenitor cells that promote nerve regeneration. In this study, the authors investigated the feasibility of intravenous administration of AFMSCs according to SDF-1 alpha expression time profiles to facilitate neural regeneration in a sciatic nerve crush injury model. Methods. Peripheral nerve injury was induced in 63 Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The animals were randomized into 1 of 3 groups: Group I, crush injury as the control; Group II, crush injury and intravenous administration of AFMSCs (5 x 10(6) cells for 3 days) immediately after injury (early administration); and Group III, crush injury and intravenous administration of AFMSCs (5 x 10(6) cells for 3 days) 7 days after injury (late administration). Evaluation of neurobehavior, electrophysiological study, and assessment of regeneration markers were conducted every week after injury. The expression of SDF-1 alpha and neurotrophic factors and the distribution of AFMSCs in various time profiles were also assessed. Results. Stromal cell-derived factor-1 alpha increased the migration and wound healing of AFMSCs in vitro, and the migration ability was dose dependent. Crush injury induced the expression of SDF-1 alpha at a peak of 10-14 days either in nerve or muscle, and this increased expression paralleled the expression of its receptor, chemokine receptor type-4 (CXCR-4). Most AFMSCs were distributed to the lung during early or late administration. Significant deposition of AFMSCs in nerve and muscle only occurred in the late administration group. Significantly enhanced neurobehavior, electrophysiological function, nerve myelination, and 'expression of neurotrophic factors and acetylcholine receptor were demonstrated in the late administration group. Conclusions. Amniotic fluid-derived mesenchymal stem cells can be recruited by expression of SDF-1 alpha in muscle and nerve after nerve crush injury. The increased deposition of AFIVISCs paralleled the expression profiles of SDF-1 alpha and its receptor CXCR-4 in either muscle or nerve. Administration of AFMSCs led to improvements in neurobehavior and expression of regeneration markers. Intravenous administration of AFMSCs may be a promising alternative treatment strategy in peripheral nerve disorder. (http://thejns.org/doi/abs/10.3171/2012.2.JNS111360