Impaired Phagocytosis in Localized Aggressive Periodontitis: Rescue by Resolvin E1

Resolution of inflammation is an active temporally orchestrated process demonstrated by the biosynthesis of novel proresolving mediators. Dysregulation of resolution pathways may underlie prevalent human inflammatory diseases such as cardiovascular diseases and periodontitis. Localized Aggressive Periodontitis (LAP) is an early onset, rapidly progressing form of inflammatory periodontal disease. Here, we report increased surface P-selectin on circulating LAP platelets, and elevated integrin (CD18) surface expression on neutrophils and monocytes compared to healthy, asymptomatic controls. Significantly more platelet-neutrophil and platelet-monocyte aggregates were identified in circulating whole blood of LAP patients compared with asymptomatic controls. LAP whole blood generates increased pro-inflammatory LTB4 with addition of divalent cation ionophore A23187 (5 µM) and significantly less, 15-HETE, 12-HETE, 14-HDHA, and lipoxin A4. Macrophages from LAP subjects exhibit reduced phagocytosis. The pro-resolving lipid mediator, Resolvin E1 (0.1–100 nM), rescues the impaired phagocytic activity in LAP macrophages. These abnormalities suggest compromised resolution pathways, which may contribute to persistent inflammation resulting in establishment of a chronic inflammatory lesion and periodontal disease progression

Subcutaneous cladribine to treat multiple sclerosis : experience in 208 patients

Objective: To report on safety and effectiveness of subcutaneous cladribine (Litak®) in multiple sclerosis (MS) patients. Methods: Litak® was offered to MS-patients irrespective of disease course. Litak® 10 mg was administered for 3–4 days during week 1. Based on lymphocyte count at week 4, patients received another 0–3 doses at week 5. A second course was administered 11 months later. Follow-up included adverse events, relapses, expanded disability status scale (EDSS), 9-hole-peg and Timed-25-foot-walking tests, no-evidence-of-disease-activity (NEDA), no-evidence-of-progression-or-active-disease (NEPAD), MRI, cerebrospinal fluid (CSF) neurofilament light chain (NfL), and lymphocyte counts. Results: In all, 208 patients received at least one course of treatment. Age at baseline was 44 (17–72) years and EDSS 0–8.5. Cladribine was generally well tolerated. One myocardial infarction, one breast cancer, and three severe skin reactions occurred without long-term sequelae. Two patients died (one pneumonia, one encephalitis). Lymphopenia grade 3 occurred in 5% and grade 4 in 0.5%. In 94 out of 116 pwMS with baseline and follow-up (BaFU) data after two treatment courses, EDSS remained stable or improved. At 18 months, 64% of patients with relapsing MS and BaFU data (n = 39) had NEDA. At 19 months, 62% of patients with progressive MS and BaFU data (n = 13) had NEPAD. Of n = 13 patients whose CSF-NfL at baseline was elevated, 77% were normalised within 12 months. Conclusions: Litak® was well tolerated. Effectiveness in relapsing MS appeared similar to cladribine tablets and was encouraging in progressive MS. Our data suggest cladribine may be safe and effective in MS-patients irrespective of their disease stage

CFTR ABLATION BY CRISPR/CAS9 IMPAIRS THE PRODUCTION OF PRO-RESOLVING LIPID MEDIATORS BY HUMAN AIRWAY EPITHELIAL CELLS

Meeting Abstract 97 - 34th Annual North American Cystic Fibrosis Conference, October 7–23, 202

Hematopoietic mobilization

OBJECTIVE: To ascertain the mobilization from the bone marrow and the functional relevance of the increased number of circulating hematopoietic stem and progenitor cells (HSPC) induced by the anti-α-4 integrin antibody natalizumab in patients with multiple sclerosis (MS). METHODS: We evaluated CD45(low)CD34+ HSPC frequency by flow cytometry in blood from 45 natalizumab-treated patients (12 of whom were prospectively followed during the first year of treatment as part of a pilot cohort and 16 prospectively followed for validation), 10 untreated patients with MS, and 24 healthy donors. In the natalizumab-treated group, we also assessed sorted HSPC cell cycle status, T- and B-lymphocyte subpopulation frequencies (n = 29), and HSPC differentiation potential (n = 10). RESULTS: Natalizumab-induced circulating HSPC were predominantly quiescent, suggesting recent mobilization from the bone marrow, and were capable of differentiating ex vivo. Circulating HSPC numbers were significantly increased during natalizumab, but heterogeneously, allowing the stratification of mobilizer and nonmobilizer subgroups. Nonmobilizer status was associated with persistence of disease activity during treatment. The frequency of B cells and CD103+CD8+ regulatory T cells persistently increased, more significantly in mobilizer patients, who also showed a specific naive/memory B-cell profile. CONCLUSIONS: The data suggest that natalizumab-induced circulating HSPC increase is the result of true mobilization from the bone marrow and has clinical and immunologic relevance. HSPC mobilization, associated with clinical remission and increased proportion of circulating B and regulatory T cells, may contribute to the treatment's mode of action; thus, HSPC blood counts could represent an early biomarker of responsiveness to natalizumab

Economic patterns of sustainable development: an analysis of absolute ecological footprint through self-organizing map

Knowledge economy, Sustainable development, Pattern recognition, SOM neural networks,