Inhibition of UVB radiation-induced tissue swelling and immune suppression by nicotinamide riboside and pterostilbene.

BACKGROUND: Environmental ultraviolet radiation has deleterious effects on humans, including sunburn and immune perturbations. These immune changes are involved in skin carcinogenesis. OBJECTIVES: To determine whether nicotinamide riboside and/or pterostilbene administered systemically inhibits inflammatory and immune effects of exposure to mid-range ultraviolet radiation. METHODS: To examine UVB radiation-induced inflammatory effects, mice were fed standard chow/water, 0.04% pterostilbene in chow and 0.2% nicotinamide riboside in drinking water, diet with nicotinamide riboside alone, or diet with pterostilbene alone. After 4 weeks, mice were exposed to UVB radiation (3500 J/m2), and 24-/48-h ear swelling was assessed. We also asked if each agent or the combination inhibits UVB radiation suppression of contact hypersensitivity in two models. Mice were fed standard diet/water or chow containing 0.08% pterostilbene, water with 0.4% nicotinamide riboside, or both for 4 weeks. Low-dose: Half the mice in each group were exposed on the depilated dorsum to UVB radiation (1700 J/m2) daily for 4 days, whereas half were mock-irradiated. Mice were immunized on the exposed dorsum to dinitrofluorobenzene 4 h after the last irradiation, challenged 7 days later on the ears with dinitrofluorobenzene, and 24-h ear swelling assessed. High dose: Mice were treated similarly except that a single dose of 10,000 J/m2 of radiation was administered and immunization was performed on the unirradiated shaved abdomen 3 days later. RESULTS: Nicotinamide riboside and pterostilbene together inhibited UVB-induced skin swelling more than either alone. Pterostilbene alone and both given together could inhibit UVB-induced immune suppression in both the low-dose and high-dose models while nicotinamide riboside alone was more effective in the low-dose model than the high-dose model. CONCLUSION: Nicotinamide riboside and pterostilbene have protective effects against UVB radiation-induced tissue swelling and immune suppression.

Endoscopic electrocauterization for management of chronic perineal sinus following abdominoperineal resection.

We present a case of a chronic perineal sinus following abdominoperineal resection with management via endoscopic electrocauterization. This patient presented with 1 year of bloody, mucus drainage from a perineal wound following abdominoperineal resection for anastomotic leak and stricture from a remote low anterior resection for T2N1 rectal cancer. We describe a novel use of endoscopic electrocautery to debride, de-epithelialize and ultimately eliminate the sinus cavity. The patient's postoperative course was uncomplicated and reported decreased drainage at 2- and 4-week postoperative follow-up. Long-term plans include sequential drain downsizing to facilitate cavity closure. Our findings suggest that endoscopic electrocauterization can safely and effectively reduce chronic perineal sinus drainage to facilitate cavity elimination, while avoiding morbidity associated with more invasive operative interventions.

Regulation of Cutaneous Immunity In Vivo by Calcitonin Gene-Related Peptide Signaling through Endothelial Cells.

Calcitonin gene-related peptide (CGRP) can bias the outcome of Ag presentation to responsive T cells in vitro away from Th1-type immunity and toward the Th2 and Th17 poles through actions on endothelial cells (ECs). To test the in vivo significance of this observation, we engineered a mouse lacking functional CGRP receptors on ECs (EC receptor activity modifying protein 1 [RAMP1] knockout mice). On percutaneous immunization to 1-fluoro-2,4-dinitrobenzene, stimulated CD4+ T cells from draining lymph nodes showed significantly reduced IL-17A expression with significantly increased IFN-γ, IL-4, and IL-22 expression at the protein and mRNA levels compared with control mice. Retinoic acid receptor-related orphan receptor γ t mRNA was significantly reduced, while mRNAs for T-box expressed in T cells and GATA binding protein 3 were significantly increased. In addition, EC RAMP1 knockout mice had significantly reduced contact hypersensitivity responses, and systemic administration of a CGRP receptor antagonist similarly inhibited contact hypersensitivity in wild-type mice. These observations provide compelling evidence that CGRP is a key regulator of cutaneous immunity through effects on ECs and suggest a novel pathway for potential therapeutic manipulation.

Treatment of Anti-GAD65 Autoimmune Encephalitis With Methylprednisolone.

Background: Anti-glutamic acid decarboxylase 65 (anti-GAD65) antibody encephalitis is a rare form of autoimmune encephalitis that can lead to severe neurologic impairment, coma, and death. Case Report: We present the case of a 54-year-old male with severely altered mental status and profound neurologic impairment who rapidly progressed to a comatose state. Because of the patient's rapidly deteriorating status, lack of yield with diagnostic testing, and lack of clinical improvement with broad empiric treatments, the clinical decision was made to treat the patient with high-dose methylprednisolone, and the treatment returned the patient to his baseline mental status. After the patient's discharge, the autoimmune encephalitis panel returned positive for anti-GAD65 antibodies. Conclusion: This case illustrates the importance of considering a diagnosis of autoimmune encephalitis for patients with rapidly deteriorating mental status. Unless contraindicated, treatment with high-dose glucocorticoids can be successful for these patients. This case also shows a potential association between hypothyroidism and anti-GAD65 antibodies.

Atypical Cause of Sepsis from Bilateral Iliopsoas Abscesses Seeded from Self-mutilation: A Case Report.

INTRODUCTION: An iliopsoas abscess (IPA) is an abscess located adjacent to the iliopsoas and iliacus muscles. Although rare, their variable clinical presentations often lead to a delay in diagnosis. CASE REPORT: We present a case of sepsis secondary to multiple IPAs that was missed despite multiple healthcare encounters. The patient had no classical risk factors for an IPA, and the abscesses were found to be seeded via hematogenous spread from self-inflicted cutting. CONCLUSION: This case illustrates the importance of obtaining a complete history, including psychiatric screen, and performing a thorough examination when evaluating patients with low back pain to rule out overlooked sources of bacteremia.

Regulation of T helper cell responses during antigen presentation by norepinephrine-exposed endothelial cells.

Dermal blood vessels and regional lymph nodes are innervated by sympathetic nerves and, under stress, sympathetic nerves release norepinephrine (NE). Exposure of primary murine dermal microvascular endothelial cells (pDMECs) to NE followed by co-culture with Langerhans cells (LCs), responsive CD4+ T-cells and antigen resulted in modulation of CD4+ T-cell responses. NE-treatment of pDMECs induced increased production of interleukin (IL)-6 and IL-17A while down-regulating interferon (IFN)-γ and IL-22 release. This effect did not require contact between pDMECs and LCs or T-cells and depended upon pDMEC production of IL-6. The presence of NE-treated pDMECs increased the proportion of CD4+ T-cells expressing intracellular IL-17A and increased IL-17A mRNA while decreasing the proportion of IFN-γ- or IL-22-expressing CD4+ T-cells and mRNA levels for those cytokines. Retinoic acid receptor-related orphan receptor gamma (ROR-γt) mRNA was significantly increased in CD4+ T-cells while T-box transcription factor (T-bet) mRNA was decreased. Intradermal administration of NE prior to hapten immunization at the injection site produced a similar bias in draining lymph node CD4+ T-cells towards IL-17A and away from IFN-γ and IL-22 production. Under stress, release of NE may have significant regulatory effects on the outcome of antigen presentation through actions on ECs with enhancement of inflammatory skin disorders involving IL-17/T helper type 17 (Th17) cells.