Flexural strength,biocompatibility, and antimicrobial activity of a polymethyl methacrylate denture resin enhanced with graphene and silver nanoparticles

Clinical Oral Investigations - The study evaluates the effect of adding graphene-Ag nanoparticles (G-AgNp) to a PMMA auto-polymerizing resin, with focus on antibacterial activity, cytotoxicity,...     

Interleukin-1 receptor type-1 in non-hematopoietic cells is the target for the pro-atherogenic effects of interleukin-1 in apoE-deficient mice

ObjectiveRecent studies indicate that regulatory T cells (Tregs) attenuate murine atherosclerosis. Since interleukin (IL)-2 induces Tregs proliferation, we tested the impact of L19-IL2, a fusion antibody specific to extra-domain B of fibronectin (ED-B) containing an active human IL-2 molecule, in experimental atherosclerosis.Methods and resultsL19-IL2 or appropriate controls were given intravenously to 6 month old Western diet-fed apoE^?/? mice on day 1, 3, and 5. Human IL-2 was detected on day 7 within atherosclerotic plaques of L19-IL2-treated mice, and magnetic resonance imaging of the plaques showed a significant adventitial gadolinium enhancement on day 7 and 13, suggesting microvascular leakage as a result of the pharmacodynamic activity of L19-IL2. Treatment with L19-IL2 significantly reduced the size of pre-established atherosclerotic plaques at the thoracic aorta (Sudan III stained area) and in the aortic root area (microscopic, morphometric analysis) on day 7 as compared to controls (L19, D1.3-IL2, NaCl) as well as compared to baseline (day 0). Tregs markers Foxp3 and CTLA4 were highly increased in plaques after L19-IL2 treatment compared to controls (p < 0.01), whereas the macrophage marker Mac3 was significantly reduced (p < 0.03). Co-treatment with IL-2-receptor blocking antibody PC61 abrogated L19-IL2-induced plaque reduction compared with IgG control (p < 0.03).ConclusionL19-IL2 delivers functional IL-2 to pre-established atherosclerotic plaques of WD-fed apoE^?/? mice resulting in significant plaque size reduction mediated by local Tregs.     

Podocyte Purinergic P2X4 Channels Are Mechanotransducers That Mediate Cytoskeletal Disorganization

Podocytes are specialized, highly differentiated epithelial cells in the kidney glomerulus that are exposed to glomerular capillary pressure and possible increases in mechanical load. The proteins sensing mechanical forces in podocytes are unconfirmed, but the classic transient receptor potential channel 6 (TRPC6) interacting with the MEC-2 homolog podocin may form a mechanosensitive ion channel complex in podocytes. Here, we observed that podocytes respond to mechanical stimulation with increased intracellular calcium concentrations and increased inward cation currents. However, TRPC6-deficient podocytes responded in a manner similar to that of control podocytes, and mechanically induced currents were unaffected by genetic inactivation of TRPC1/3/6 or administration of the broad-range TRPC blocker SKF-96365. Instead, mechanically induced currents were significantly decreased by the specific P2X purinoceptor 4 (P2X₄) blocker 5-BDBD. Moreover, mechanical P2X₄ channel activation depended on cholesterol and podocin and was inhibited by stabilization of the actin cytoskeleton. Because P2X₄ channels are not intrinsically mechanosensitive, we investigated whether podocytes release ATP upon mechanical stimulation using a fluorometric approach. Indeed, mechanically induced ATP release from podocytes was observed. Furthermore, 5-BDBD attenuated mechanically induced reorganization of the actin cytoskeleton. Altogether, our findings reveal a TRPC channel-independent role of P2X₄ channels as mechanotransducers in podocytes.     

Acute lymphoblastic leukemia in the elderly: The Edouard Herriot Hospital experience

Data on all patients with acute lymphoblastic leukemia (ALL) aged 60 or older, referred to our institution over a 18-year period, were studied to determine the incidence and range of clinical and biological subtypes, and the outcome of different therapeutic approaches. Sixty-nine ALL cases (median age: 68 years) were diagnosed between 1980 and 1998 (18% of all adult ALL seen during this period). Ten of them (14%) had a past history of previous malignancy. Karyotypic analysis was performed successfully in 42 cases. Ten patients were diagnosed as Philadelphia chromosome positive (Ph(+)) ALL. Immunophenotyping was performed in 63 cases. Fifty-six patients had B-cell lineage ALL. T lymphoid markers were observed only in 5 cases. Co-expression of myeloid markers was observed in 19% of tested cases. Five patients died before any chemotherapy could be given. All other patients received "curative" treatment according to different protocols used during the period of study. Overall complete remission (CR) rate of these patients was 62% (95% confidence interval (CI): 50-74%). Thirty-nine patients achieved CR after one course of chemotherapy and 4 patients after salvage therapy. Median disease-free survival (DFS) of the entire cohort was 8.3 months (95% CI: 5-12.8 months) and median overall survival was 7 months (95% CI: 6-10 months). In multivariate analysis, the presence of hemorrhage (P = 0.02) was a poor prognostic for CR achievement. Higher WHO performance status (P = 0.003) and the presence of hemorrhage (P = 0.01) at diagnosis were poor prognostics for overall survival. When patients were stratified into three groups according to the time of admission, survival appeared significantly longer for patients admitted between July 1992 and December 1998 (median overall survival at 10 months) than for patients admitted before July 1992 (P = 0.04). "Age-adapted" therapy appeared superior to "young adult-like" therapy in terms of CR rate (96% versus 60%; P = 0.007). However, "age-adapted" therapy did not show any advantage in terms of DFS or overall survival, making the difference in CR rates questionable. We conclude that the pejorative overall outcome in elderly ALL points to the need for new therapeutic trials taking into account the specific characteristics of ALL in this age group.     

IL-17 in cutaneous lupus erythematosus

BackgroundLupus erythematosus (LE) is a heterogeneous disease with broad clinical spectrum from cutaneous to visceral and systemic inflammation. IL-17 isoforms (IL-17A and IL-17F) are proinflammatory cytokines with unclear implications in lupus erythematosus pathogenesis. In this study we focused upon IL-17 in normal and modified lupus skin with a correlative study between local and serological expression.Material and methods89 subjects were recruited and divided in 5 groups—10 patients with psoriasis (disease control group), 13 healthy controls, 26 with discoid chronic lupus (DLE), 23 with systemic lupus erythematosus (SLE) and 17 with subacute lupus erythematosus (SCLE). Blood samples and skin punched-biopsy specimens were performed. Serum IL-17A, IL-17F, and IL-23 concentrations were determined by ELISA. Skin IL-17A and CD4 expression were evaluated by immunohistochemistry.ResultsImmunohistochemical expression of IL-17A was higher in DLE, SCLE and SLE patients than in negative control subjects (all p < 0.05). Serum IL-17A concentrations were higher in DLE and SLE patients than in negative controls (p < 0.05). Serum IL-17A levels were similar in SCLE and negative controls (p > 0.05). Serum IL-17F concentrations were higher in DLE, SCLE and SLE patients than in healthy controls (all p < 0.05). In DLE, SCLE, SLE patients and healthy controls we observed comparable levels of IL-23 (p > 0.05). Serum anti Ro antibodies correlate with IL-17A+ lymphocytes from SCLE lesion and SLE normal skin (all p < 0.05).ConclusionIL-17 isoforms (IL-17A and IL-17F) are implicated in SLE but also in DLE and SCLE immunopathogenesis.     

Inflammatory reaction in chronic periodontopathies in patients with diabetes mellitus. Histological and immunohistochemical study

Chronic periodontopathies and diabetes mellitus are two clinical entities, which reciprocally condition one another. The periodontal disease is considered a major complication, which induces an unfavorable evolution of diabetes mellitus. Diabetes mellitus is an endocrine disease which favors the occurrence of periodontopathy through gum's microvascular disorders, the selection and development of an aggressive bacterial plaque and through an exaggerate inflammatory response to the microflora within the oral cavity. Both diabetes mellitus and periodontal disease have an increasing incidence in the whole world. Development of periodontopathy is related to the aggression of bacterial flora in dental plaque, flora that is influenced on its turn by the evolution of diabetes mellitus. In our study, we have evaluated the inflammatory reaction in periodontium in patients with slowly and progressive periodontitis in patients with diabetes mellitus who had diabetes longer than five years. It has been found that all patients presented a chronic inflammatory infiltrate, abundant, with round mononuclear cells of lymphocyte, plasma cells and macrophage type, with non-homogenous arrangement, more intensely where the covering epithelium presented erosions or necrotic areas. Out of the immunity system cells, the most numerous where of T-lymphocytes type.