Effects of Eltrombopag on In Vitro Macrophage Polarization in Pediatric Immune Thrombocytopenia

Immune Thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibodies-mediated platelet destruction, a prevalence of M1 pro-inflammatory macrophage phenotype and an elevated T helper 1 and T helper 2 lymphocytes (Th1/Th2) ratio, resulting in impairment of inflammatory profile and immune response. Macrophages are immune cells, present as pro-inflammatory classically activated macrophages (M1) or as anti-inflammatory alternatively activated macrophages (M2). They have a key role in ITP, acting both as effector cells, phagocytizing platelets, and, as antigen presenting cells, stimulating auto-antibodies against platelets production. Eltrombopag (ELT) is a thrombopoietin receptor agonist licensed for chronic ITP to stimulate platelet production. Moreover, it improves T and B regulatory cells functions, suppresses T-cells activity, and inhibits monocytes activation. We analyzed the effect of ELT on macrophage phenotype polarization, proposing a new possible mechanism of action. We suggest it as a mediator of macrophage phenotype switch from the M1 pro-inflammatory type to the M2 anti-inflammatory one in paediatric patients with ITP, in order to reduce inflammatory state and restore the immune system function. Our results provide new insights into the therapy and the management of ITP, suggesting ELT also as immune-modulating drug.     

Notch Signaling Regulation in Autoinflammatory Diseases

Notch pathway is a highly conserved intracellular signaling route that modulates a vast variety of cellular processes including proliferation, differentiation, migration, cell fate and death. Recently, the presence of a strict crosstalk between Notch signaling and inflammation has been described, although the precise molecular mechanisms underlying this interplay have not yet been fully unravelled. Disruptions in Notch cascade, due both to direct mutations and/or to an altered regulation in the core components of Notch signaling, might lead to hypo- or hyperactivation of Notch target genes and signaling molecules, ultimately contributing to the onset of autoinflammatory diseases. To date, alterations in Notch signaling have been reported as associated with three autoinflammatory disorders, therefore, suggesting a possible role of Notch in the pathogenesis of the following diseases: hidradenitis suppurativa (HS), Behçet disease (BD), and giant cell arteritis (GCA). In this review, we aim at better characterizing the interplay between Notch and autoinflammatory diseases, trying to identify the role of this signaling route in the context of these disorders.     

Generation of Nanoparticles with a Nebulizer-Cyclone System

A cyclone was used to modify the droplet output with a three-jet Collison nebulizer. The cyclone-nebulizer system was tested by producing ammonium fluorescein particles from a liquid suspension. The particle size distribution produced with the cyclone was smaller and narrower than that produced without the cyclone. Thus, the cyclone effectively removed the large droplets produced by the nebulizer. The nebulizer-cyclone system reduced the GSD of the output aerosol from 1.7 to 1.4. At the input pressures greater than 138 kPa, the concentration of 10–60 nm particles was greater with the cyclone than without the cyclone. These results are consistent with the shattering of large droplets within the cyclone and re-entrainment of these small secondary droplets. Optimization of the system using cyclone modeling to enhance the sharpness of cut, operational improvements, and decreased venting could maximize the output of tailored distributions of nanoparticles for various applications.     

Electro-tactile device for material texture simulation

This paper deals with the simulation of material texture by means of electro-tactile stimuli, which directly derive from real material properties. The research presents a novel tactile display by its hardware and software system architecture and the elaboration procedure to generate the stimulating signals, and validates the adopted simulation strategy by experimental testing. The tactile system elaborates data from scans of real material samples and generates electrical stimuli to reproduce roughness and texture coarseness sensations. It also adds a coherent sound feedback to improve the realism of the simulation. The research defines also an experimental protocol based on the theory of Psychophysics to carry out system calibration and tests with users. The scope is to validate the proposed tactile system as a new tool for material simulation, which can be adopted for material virtual prototyping in several fields (product design, textile and clothing, gaming and entertainment, virtual museum, rehabilitation, etc.). Experimentations have been carried out to measure the users’ response to our different material classes (wood, paper, rubber and textile fabric). Experimental results concern how good the adopted simulation approach is and the analysis of the human tactile perception simulated by the system. Main findings relate to the system performance and the users’ response in terms of signal recognition and material class discrimination.     

电位滴定分析ASP驱采出液中表面活性剂浓度

以十二烷基磺酸钠为例,考察了利用电位滴定方法分析ASP三元复合驱采出液中表面活性剂浓度时,pH值、盐度、聚合物含量、石油酸皂浓度等因素对分析结果的影响,研究出因石油酸皂和聚合物的存在导致结果偏高的消除方法,并对方法的检出限进行研究。该方法为ASP三元驱中十二烷基磺酸钠类阴离子表面活性剂浓度的分析提供了参考。     

Antioxidant Activity of Free and Bound Compounds in Quinoa (Chenopodium quinoa Willd.) Seeds in Comparison with Durum Wheat and Emmer

Abstract: Antioxidant activity (AA) of quinoa (Chenopodium quinoa Willd.) seeds, as well as of durum wheat (Triticum turgidum L. ssp. durum Desf.) and of emmer (T. turgidum L. ssp. dicoccum Schübler) grains, was evaluated by studying hydrophilic (H), lipophilic (L), free‐soluble (FSP) and insoluble‐bound (IBP) phenolic extracts using the new lipoxygenase/4‐nitroso‐N,N‐dimethylaniline (LOX/RNO) method, able to simultaneously detect different antioxidant mechanisms, as well as using the Oxygen Radical Absorbance Capacity (ORAC) and the Trolox Equivalent Antioxidant Capacity (TEAC) assays, which measure the scavenging activity against peroxyl and ABTS [2,2′‐azino‐bis‐(3‐ethylbenzothiazoline‐6‐sulfonate)] radicals, respectively. The species under study were compared with respect to the sum of AA values of H, L and FSP extracts (AA_H+L+FSP), containing freely solvent‐soluble antioxidants, and AA values of IBP extracts (AA_IBP), representing the phenolic fraction ester‐linked to insoluble cell wall polymers. The LOX/RNO and ORAC methods measured in quinoa flour a remarkable AA_H+L+FSP higher than durum wheat, although lower than emmer; according to the same assays, the IBP component of quinoa resulted less active than the durum wheat and emmer ones. The TEAC protocol also revealed a high AA_H+L+FSP for quinoa. Interestingly, the ratio AA_H+L+FSP/AA_H+L+FSP+IBP, as evaluated by the LOX/RNO and ORAC assays, resulted in quinoa higher than that of both durum wheat and emmer, and much higher than durum wheat, according to the TEAC protocol. This may suggest that antioxidants from quinoa seeds may be more readily accessible with respect to that of both the examined wheat species. Practical Applications: Quinoa seeds may represent an excellent source of natural antioxidant compounds and, in particular, of the free‐soluble antioxidant fraction. These compounds may improve nutritive and health‐beneficial properties of quinoa‐based gluten‐free products, thus expanding interest for quinoa utilization from celiac patients to the general population.     

What is 'minimally invasive' coronary bypass surgery? Experience with a variety of surgical revascularization procedures for single-vessel disease

BACKGROUND: Although the use of small incisions is theoretically appealing, it has been argued that the true advantage of minimally invasive approaches to myocardial revascularization lies in the avoidance of cardiopulmonary bypass. METHODS: Of 25 patients referred for surgical revascularization of single-vessel coronary disease, 20 elected to undergo a minimally invasive coronary artery bypass grafting (MICABG) procedure, while 5 opted to have conventional surgery with cardiopulmonary bypass (CPB). Patients having MICABG underwent single-vessel revascularization without CPB, via limited anterior thoracotomy, hemisternotomy, or median sternotomy. Intraoperatively, hemodynamics, anastomotic time, and total operative time were recorded. Postoperatively, length of hospital stay, incidence of myocardial infarction, indexes of end-organ function, and morbidity rates were recorded. In addition, patient questionnaires were used to assess subjective end points such as postoperative pain, wound drainage, and quality of life. RESULTS: Fifteen of 20 patients undergoing MICABG underwent revascularization without CPB, while 4 were converted to standard coronary artery bypass grafting with CPB due to technical reasons and 1 for intraoperative ventricular fibrillation. Patients undergoing MICABG had no perioperative myocardial infarctions, while those having CPB had two infarctions (20%). Furthermore, there were no differences in length of stay or postoperative morbidity among the various approaches, while the MICABG procedures, especially via median sternotomy, were associated with shorter operative times. CONCLUSIONS: The advantage of MICABG lies mainly in the avoidance of CPB. Thus, we advocate that surgeons initially utilize the median sternotomy and limited skin incision for MICABG to assure adequate exposure, technical precision, and patient safety. After a reasonable level of technical proficiency and experience are attained, the limited anterior thoracotomy approach can be used.     

Platelet transfusions are associated with the development of anti-major histocompatibility complex class I antibodies in patients with left ventricular assist support

BACKGROUND: Preformed anti-human leukocyte antigen (HLA) antibodies delay heart transplantation in patients with left ventricular assist devices (LVAD) because of difficulty in finding crossmatch-negative donors. These antibodies may also be associated with adverse outcome after transplantation. METHODS: In a retrospective analysis of 40 patients with LVAD at Columbia-Presbyterian Medical Center between 1990 to 1996, age, sex, diagnosis, race, duration of support, transfusions, and infections were studied by univariate and multivariate analysis as predictors for development of either anti-HLA class I (anti-I) or anti-HLA class II (anti-II) immunoglobulin G (IgG) or M (IgM) antibodies. RESULTS: Eighteen (45%) patients had development of anti-I and 20 (50%) had development of anti-II antibodies over the study period. Median time for LVAD support was 142 days (range 35 to 439). Only total number of perioperative platelet transfusions predicted the development of anti-I IgG antibodies (p = .04). No other associations were found for development of anti-I IgM or anti-II antibodies of either IgG or IgM specificity. Patients who had development of anti-I IgG received a mean of 13.9 (SE +/- 2.6) units of platelets compared with a mean of 7.7 (SE +/- 2.3) units in those who did not (p = .01). By Kaplan-Meier analysis, at the median duration of follow-up, 8% of patients receiving < 6 units were predicted to have development of anti-I antibodies compared with 63% receiving > 6 units (p = .002). In the last 7 patients, leukocyte filters were used to decrease the antigenic load during platelet and red blood cell transfusions. Only 1 of 7 (14%) patients had development of anti-HLA antibodies compared with 31 of 33 (94%) in whom filters were not used (p < .005). CONCLUSIONS: These results indicate that platelet transfusion during LVAD implantation is a risk factor associated with development of HLA class I IgG antibodies. Use of leukocyte filters during platelet transfusion may decrease the risk of development of anti-HLA antibodies.