Resolvin D1 and Aspirin-Triggered Resolvin D1 Regulate Histamine-stimulated Conjunctival Goblet Cell Secretion

Resolution of inflammation is an active process mediated by pro-resolution lipid mediators. Since resolvin (Rv) D1 is produced in the cornea, pro-resolution mediators could be effective in regulating inflammatory responses to histamine in allergic conjunctivitis. Two key mediators of resolution are the D-series resolvins RvD1 or aspirin-triggered RvD1 (AT-RvD1). We used cultured conjunctival goblet cells to determine whether histamine actions can be terminated during allergic responses. We found cross-talk between two types of G protein-coupled receptors, as RvD1 interacts with its receptor GPR32 to block histamine-stimulated H1 receptor increases in intracellular [Ca2+] ([Ca2+]i) preventing H1 receptor-mediated responses. In human and rat conjunctival goblet cells RvD1 and AT-RvD1 each block histamine-stimulated secretion by preventing its increase in [Ca2+]i and activation of extracellular regulated protein kinase (ERK)1/2. We suggest that D-series resolvins regulate histamine responses in the eye and offer new treatment approaches for allergic conjunctivitis or other histamine-dependent pathologies

Aquaporins in Brain Edema and Neuropathological Conditions

The aquaporin (AQP) family of water channels are a group of small, membrane-spanning proteins that are vital for the rapid transport of water across the plasma membrane. These proteins are widely expressed, from tissues such as the renal epithelium and erythrocytes to the various cells of the central nervous system. This review will elucidate the basic structure and distribution of aquaporins and discuss the role of aquaporins in various neuropathologies. AQP1 and AQP4, the two primary aquaporin molecules of the central nervous system, regulate brain water and CSF movement and contribute to cytotoxic and vasogenic edema, where they control the size of the intracellular and extracellular fluid volumes, respectively. AQP4 expression is vital to the cellular migration and angiogenesis at the heart of tumor growth; AQP4 is central to dysfunctions in glutamate metabolism, synaptogenesis, and memory consolidation; and AQP1 and AQP4 adaptations have been seen in obstructive and non-obstructive hydrocephalus and may be therapeutic targets

Acute necrotizing encephalopathy of childhood secondary to parainfluenza infection: A review of two cases

Introduction: Acute necrotizing encephalopathy (ANE) of childhood is a rare inflammatory syndrome, classically associated with preceding febrile illness and followed by fulminant neurological deterioration including encephalopathy, seizures, and focal neurological deficits with multifocal lesions of the thalami, rostral brainstem, and cerebral and cerebellar gray and white matter. ANE is distinctly associated with significant rates of neurological sequelae and death. Multiple infectious and parainfectious etiologies have been associated with ANE, notably influenza A. Case Report: We report two cases of ANE associated with parainfluenza infection. Both children were treated with high-dose methylprednisolone and intravenous immunoglobulin, and one treated with tocilizumab. However, both patients suffered rapid neurological deterioration and death despite aggressive intervention. Conclusion: We present two cases of ANE with rapid neurological deterioration and death despite aggressive medical therapy. Rapid treatment with immunomodulatory treatments can lead to symptomatic recovery of variable degree in some patients. While high-dose steroids, intravenous immunoglobulin, and plasma exchange are common therapies for ANE, some case reports have suggested interleukin-6 (IL-6) blockade with tocilizumab can be beneficial. We report the nineteenth documented child in pediatric literature treated for ANE with tocilizumab, who did not respond to treatment, suggesting the response is heterogeneous and warrants additional investigation