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Diabetic retinopathy (DR) is one of the most common complications of Diabetes Mellitus (DM) and is directly associated with inflammatory processes. Currently, neuro-inflammation is considered an early event in DR and proceeds via microglia polarization. A hallmark of DR is the presence of retinal reactive gliosis. Here we report the beneficial effect of (S S,1 R)-1-docecylsulfiny-5 N ,6 O -oxomethylidenenojirimycin ((Ss)-DS-ONJ), a member of the sp2-iminosugar glycolipid (sp2-IGL) family, by decreasing iNOS and inflammasome activation in Bv.2 microglial cells exposed to pro-inflammatory stimuli. Moreover, pretreatment with (Ss)-DS-ONJ increased Heme-oxygenase (HO)-1 as well as interleukin 10 (IL10) expression in LPS-stimulated microglial cells, thereby promoting M2 (anti-inflammatory) response by the induction of Arginase-1. The results strongly suggest that this is the likely molecular mechanism involved in the anti-inflammatory effects of (S S)-DS-ONJ in microglia. (S S)-DS-ONJ further reduced gliosis in retinal explants from type 1 diabetic BB rats, which is consistent with the enhanced M2 response. In conclusion, targeting microglia polarization dynamics in M2 status by compounds with anti-inflammatory activities offers promising therapeutic interventions at early stages of DR. [ABSTRACT FROM AUTHOR]

A case involving the incidental diagnosis of multiple myeloma (MM) due to interference in the 25-hydroxy-vitamin D (25(OH) vitamin D) immunoassay is presented. The patient, under the care of rheumatology and receiving treatment with alendronic acid and vitamin D supplements, was referred to endocrinology for investigation of acromegaly. Acromegaly was subsequently ruled out; however, during the investigations, consistently elevated levels of 25(OH) vitamin D were noted, raising suspicion of vitamin D resistance syndrome. The laboratory and endocrinology teams engaged in discussions, and following the cessation of medication, repeated analyses for 25(OH) vitamin D and a single analysis of 1,25-dihydroxy-vitamin D levels were requested, yielding high and normal results, respectively. The laboratory conducted a three-step interference investigation, ultimately identifying a high molecular weight molecule responsible for the initially elevated 25(OH) vitamin D levels. Due to the clinical presentation of back pain, a proteinogram was requested, revealing a monoclonal band of 36 g/L. Subsequent free light chain analysis indicated an elevated ratio. With three risk factors identified, this was classified as an established MM and urgently referred to haematology for correct management. Laboratory assay interferences have the potential to disrupt the accurate diagnostic workup of patients. Collaborative discussions between laboratory and clinical teams regarding such cases aid in directing the diagnostic pathway appropriately, facilitating prompt and proper diagnosis and management. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is one of the most common complications of Diabetes Mellitus (DM) and is directly associated with inflammatory processes. Currently, neuro-inflammation is considered an early event in DR and proceeds via microglia polarization. A hallmark of DR is the presence of retinal reactive gliosis. Here we report the beneficial effect of ( S S ,1 R )-1-docecylsulfiny-5 N ,6 O -oxomethylidenenojirimycin (( Ss )-DS-ONJ), a member of the sp 2 -iminosugar glycolipid (sp 2 -IGL) family, by decreasing iNOS and inflammasome activation in Bv.2 microglial cells exposed to pro-inflammatory stimuli. Moreover, pretreatment with ( Ss )-DS-ONJ increased Heme-oxygenase (HO)-1 as well as interleukin 10 (IL10) expression in LPS-stimulated microglial cells, thereby promoting M2 (anti-inflammatory) response by the induction of Arginase-1. The results strongly suggest that this is the likely molecular mechanism involved in the anti-inflammatory effects of ( S S )-DS-ONJ in microglia. ( S S )-DS-ONJ further reduced gliosis in retinal explants from type 1 diabetic BB rats, which is consistent with the enhanced M2 response. In conclusion, targeting microglia polarization dynamics in M2 status by compounds with anti-inflammatory activities offers promising therapeutic interventions at early stages of DR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cano-Cano, Alcalde-Estévez, Gómez-Jaramillo, Iturregui, Sánchez-Fernández, García Fernández, Ortiz Mellet, Campos-Caro, López-Tinoco, Aguilar-Diosdado, Valverde and Arroba.)