Primary intramedullary spinal cord non-Hodgkin lymphoma: Case report and review of the literature

Introduction: Primary intramedullary spinal cord lymphomas are extremely rare, occurring mainly in immune compromised patients. Case report: We report a case of a 43 years old patient admitted with spinal cord compression. Spinal MRI revealed two thoracic intramedullary tumours. The patients underwent surgery and we performed resection of both primary intramedullary tumours, with favourable neurological outcome. The histopathologic exam was non-Hodgkin lymphoma. The patient underwent adjuvant radiotherapy. Two months later the patient presented thoracic and cerebellar drop metastases, confirmed histopathologically. Conclusions: The diagnosis of primary intramedullary spinal lymphoma must be kept in mind in patients with myelopathy. Surgery is needed to provide histopathological samples for positive diagnosis and spinal decompression. Primary intramedullary spinal lymphomas have a propensity to disseminate along the neuraxis

Hydrogen sulfide inhibits aortic valve calcification in heart via regulating RUNX2 by NF-κB, a link between inflammation and mineralization

This is the final version. Available on open access from Elsevier via the DOI in this recordIntroduction: Hydrogen sulfide (H2S) was revealed to inhibit aortic valve calcification and inflammation was implicated in the pathogenesis of calcific aortic valve disease (CAVD). Objectives: We investigate whether H2S inhibits mineralization via abolishing inflammation. Methods and results: Expression of pro-inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) were increased in patients with CAVD and in calcified aortic valve of ApoE-/- mice. Administration of H22S releasing donor (4-methoxyphenyl piperidinylphosphinodithioc acid (AP72)) exhibited inhibition on both calcification and inflammation in aortic valve of apolipoprotein E knockout mice (ApoE-/-) mice is reflected by lowering IL-1β and TNF-α levels. Accordingly, AP72 prevented the accumulation of extracellular calcium deposition and decreased nuclear translocation of nuclear factor-κB (NF-κB) in human valvular interstitial cells (VIC). This was also accompanied by reduced cytokine response. Double-silencing of endogenous H2S producing enzymes, Cystathionine gamma-lyase (CSE) and Cystathionine beta-synthase (CBS) in VIC exerted enhanced mineralization and higher levels of IL-1β and TNF-α. Importantly, silencing NF-κB gene or its pharmacological inhibition prevented nuclear translocation of runt-related transcription factor 2 (Runx2) and subsequently the calcification of human VIC. Increased levels of NF-κB and Runx2 and their nuclear accumulation occurred in ApoE-/- mice with a high-fat diet. Administration of AP72 decreased the expression of NF-κB and prevented its nuclear translocation in VIC of ApoE-/- mice on a high-fat diet, and that was accompanied by a lowered pro-inflammatory cytokine level. Similarly, activation of Runx2 did not occur in VIC of ApoE-/- mice treated with H2S donor. Employing Stimulated Emission Depletion (STED) nanoscopy, a strong colocalization of NF-κB and Runx2 was detected during the progression of valvular calcification. Conclusions: Hydrogen sulfide inhibits inflammation and calcification of aortic valve. Our study suggests that the regulation of Runx2 by hydrogen sulfide (CSE/CBS) occurs via NF-κB establishing a link between inflammation and mineralization in vascular calcification.Hungarian Academy of SciencesHungarian GovernmentEuropean UnionEuropean Regional Development Fund (ERDF)Medical Research Council (MRC)Brian Ridge ScholarshipMinistry for Innovation and Technology, Hungar

Hydrogen sulfide inhibits calcification of heart valves; implications for calcific aortic valve disease

This is the final version. Available from the publisher via the DOI in this record.Background and Purpose: Calcification of heart valves is a frequent pathological finding in chronic kidney disease and in elderly patients. Hydrogen sulfide (H2S) may exert anti-calcific actions. Here we investigated H2S as an inhibitor of valvular calcification and to identify its targets in the pathogenesis. Experimental Approach: Effects of H2S on osteoblastic transdifferentiation of valvular interstitial cells (VIC) isolated from samples of human aortic valves were studied using immunohistochemistry and western blots. We also assessed H2S on valvular calcification in apolipoprotein E-deficient (ApoE−/−) mice. Key Results: In human VIC, H2S from donor compounds (NaSH, Na2S, GYY4137, AP67, and AP72) inhibited mineralization/osteoblastic transdifferentiation, dose-dependently in response to phosphate. Accumulation of calcium in the extracellular matrix and expression of osteocalcin and alkaline phosphatase was also inhibited. RUNX2 was not translocated to the nucleus and phosphate uptake was decreased. Pyrophosphate generation was increased via up-regulating ENPP2 and ANK1. Lowering endogenous production of H2S by concomitant silencing of cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS) favoured VIC calcification. analysis of human specimens revealed higher Expression of CSE in aorta stenosis valves with calcification (AS) was higher than in valves of aortic insufficiency (AI). In contrast, tissue H2S generation was lower in AS valves compared to AI valves. Valvular calcification in ApoE−/− mice on a high-fat diet was inhibited by H2S. Conclusions and Implications: The endogenous CSE-CBS/H2S system exerts anti-calcification effects in heart valves providing a novel therapeutic approach to prevent hardening of valves