Inhalable fucoidan microparticles combining two antitubercular drugs with potential application in pulmonary tuberculosis therapy

The pulmonary delivery of antitubercular drugs is a promising approach to treat lung tuberculosis. This strategy not only allows targeting the infected organ instantly, it can also reduce the systemic adverse effects of the antibiotics. In light of that, this work aimed at producing fucoidan-based inhalable microparticles that are able to associate a combination of two first-line antitubercular drugs in a single formulation. Fucoidan is a polysaccharide composed of chemical units that have been reported to be specifically recognised by alveolar macrophages (the hosts of Mycobacterium). Inhalable fucoidan microparticles were successfully produced, effectively associating isoniazid (97%) and rifabutin (95%) simultaneously. Furthermore, the produced microparticles presented adequate aerodynamic properties for pulmonary delivery with potential to reach the respiratory zone, with a mass median aerodynamic diameter (MMAD) between 3.6-3.9 mu m. The formulation evidenced no cytotoxic effects on lung epithelial cells (A549), although mild toxicity was observed on macrophage-differentiated THP-1 cells at the highest tested concentration (1 mg/mL). Fucoidan microparticles also exhibited a propensity to be captured by macrophages in a dose-dependent manner, as well as an ability to activate the target cells. Furthermore, drug-loaded microparticles effectively inhibited mycobacterial growth in vitro. Thus, the produced fucoidan microparticles are considered to hold potential as pulmonary delivery systems for the treatment of tuberculosis.Portuguese Foundation for Science and Technology [PTDC/DTP-FTO/0094/2012, UID/Multi/04326/2013, UID/BIM/04773/2013]; CAPES-Brazil [BEX 1168/13-4

Evaluation of bioactivity of fucoidan from laminaria with in vitro human cell cultures (THP-1)

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesBackground: Seaweeds represent one of the few remaining food sources available globally which are not being fully utilized or even over utilized. Kelps (Laminaria spp.) are one of the numerous species of brown seaweeds, a popular marine vegetable, which has been used as a source of iodine and minerals for centuries. Kelps contain anionic polysaccharides called fucoidans heteroglycans with L-fucose units. Their monosaccharide composition, physicochemical and bioactive properties vary between seaweed species. The objective of this work was to evaluate the bioactive properties of laminaria fucoidan (L. digitata and L. hyperborea) toward THP-1 macrophages, a human macrophage like cell line, and investigate its potential antioxidant and immunomodulatory characteristics. Methods: THP-1 macrophages were incubated with five fucoidan concentrations. The Oxygen Radical Absorbance Capacity (ORAC) assay was determined for cell lysates and for the fucoidan extract, in addition to Total Polyphenol Content (TPC). Cytotoxicity of fucoidan was assessed by light microscopy, followed by XTT proliferation assay. Enzyme-linked immunosorbant assays (ELISA) were performed to determine concentrations of the secreted tumor necrosis factor a (TNF-a), interleukin 6 (IL-6), and interleukin 10 (IL-10). Results: Fucoidan did not affect macrophage ability to scavenge oxygen radicals (ORAC) confirming its antioxidant properties toward activated macrophages. The laminaria fucoidan extract at 100 mu g/ml concentration lowered macrophage viability. Lower concentrations of laminaria fucoidan did not have impact on cell viability. Very low concentration of fucoidan at 0.1 mu g/ml triggered secretion of TNF-alpha. However, IL-6 and interleukin IL-10 were expressed when concentration of applied fucoidan was 10 mu g/ml indicating bioactivity of laminaria fucoidan through immunomodulatory actions. Conclusions: The study demonstrated how laminaria fucoidan may have bioactive properties towards THP-1 macrophages. Changes in cytokine secretion between pro-inflammatory (TNF-alpha, and IL-6) and anti-inflammatory (IL-10) cytokines confirmed bioactivity of the laminaria fucoidan extracts.University of Iceland Research Fun

Influence of religiosity on the quality of life and on pain intensity in chronic pancreatitis patients after neurolytic celiac plexus block:Case-controlled study

The quality of life in patients with chronic pancreatitis (CP) is reduced due to their suffering of high levels of pain. It has been presented that quality of life can also be linked to religiosity and/or spirituality. The aim of this study is to assess the influence of religious practices on the quality of life and on the subjective level of pain in CP patients. Ninety-two patients (37 women and 55 men) with chronic pancreatitis were treated invasively for pain with neurolytic celiac plexus block (NCPB). The religiosity of the patients was recorded and served as a dichotomizer. Group 1 was for patients who claimed to have no contact with the church or to have very sporadic contact (N = 35 patients). Group 2 was for patients who claimed to have deep faith and were regular participants at church activities (N = 57 patients). Visual analogue scale was used to assess pain, while the quality of life was measured by using QLQ C-30 questionnaire adapted for chronic pancreatitis patients in Polish population. The patients were assessed prior to the pain-relieving intervention and subsequently 2 and 8 weeks after it. The intensity of pain was reduced in both groups significantly after performing the NCPB. Patients who declared a deep faith reported higher level of pain on the VAS scale prior to intervention than non-religious patients. Quality of life in both groups of patients significantly improved after NCPB. Following NCPB, global quality of life in patients who declared higher religiosity/church attendance was significantly higher (79.88) than for those patients who have no contact or sporadic contact with the church (44.21, P < 0.05). NCPB resulted in significant reduction of pain and increase in quality of life in both groups of patients with CP. Nevertheless, in the group declaring higher religiosity/church attendance, reported pain was higher, but, despite that, quality of life better. It may be concluded that religious practices might serve as an additional factor improving quality of life and coping in patients suffering from chronic pancreatitis. Keywords Chronic pancreatitis Pain Coping Religiosity Neurolytic coeliac plexus block NCPB Spiritualit

First Spitzer Space Telescope Observations of Magnetic Cataclysmic Variables: Evidence for Excess Emission at 3--8 microns

We present the first observations of magnetic cataclysmic variables with the Spitzer Space Telescope. We used the Infrared Array Camera to obtain photometry of the polars EF Eri, GG Leo, V347 Pav, and RX J0154.0-5947 at 3.6, 4.5, 5.8, and 8.0 $\mu$m. In all of our targets, we detect excess mid-infrared emission over that expected from the component stars alone. We explore the origin of this IR excess by examining bremsstrahlung, cyclotron emission, circumbinary dust, and L/T brown dwarf secondary stars. Bremsstrahlung and cyclotron emission appear unlikely to be significant contributors to the observed fluxes. At present, the most likely candidate for the excess emission is dust that is probably located in a circumbinary disk with an inner temperature near 800 K. However, a simple dust disk plus any reasonable low mass or brown dwarf-like secondary star is unable to fully explain the observed flux densities in the 3--8 $\mu$m region.Comment: Accepted to ApJ Letter

City tourism destinations and terrorism – a worrying trend for now, but could it get worse?

The advent of the tragic events of 9/11 in the USA and subsequent terrorism attacks in global tourism cities such as Paris, Brussels, Berlin, Istanbul, London and Barcelona, to mention but a few, have resulted in major challenges for the tourism sector, including the events industry in cities. Although terrorism attacks continue to increase in number and magnitude, the phenomenon is hardly new historically, and scholars have suggested that the concept of organised terror on a wide-scale stretches as far back as the French Revolution in the eighteenth century or even some of the war tactics employed by Genghis Khan, ruler of the largest empire in history in the thirteenth century (see Edgell and Swanson, 2019). Academic research on the impact of terrorism on tourism has developed substantially over the last two decades both in terms of its breadth and depth as a reflection of the new world order we continue to navigate today

Differences in estimates of size distribution of beryllium powder materials using phase contrast microscopy, scanning electron microscopy, and liquid suspension counter techniques

Accurate characterization of the physicochemical properties of aerosols generated for inhalation toxicology studies is essential for obtaining meaningful results. Great emphasis must also be placed on characterizing particle properties of materials as administered in inhalation studies. Thus, research is needed to identify a suite of techniques capable of characterizing the multiple particle properties (i.e., size, mass, surface area, number) of a material that may influence toxicity. The purpose of this study was to characterize the morphology and investigate the size distribution of a model toxicant, beryllium. Beryllium metal, oxides, and alloy particles were aerodynamically size-separated using an aerosol cyclone, imaged dry using scanning electron microscopy (SEM), then characterized using phase contrast microscopy (PCM), a liquid suspension particle counter (LPC), and computer-controlled SEM (CCSEM). Beryllium metal powder was compact with smaller sub-micrometer size particles attached to the surface of larger particles, whereas the beryllium oxides and alloy particles were clusters of primary particles. As expected, the geometric mean (GM) diameter of metal powder determined using PCM decreased with aerodynamic size, but when suspended in liquid for LPC or CCSEM analysis, the GM diameter decreased by a factor of two (p < 0.001). This observation suggested that the smaller submicrometer size particles attached to the surface of larger particles and/or particle agglomerates detach in liquid, thereby shifting the particle size distribution downward. The GM diameters of the oxide materials were similar regardless of sizing technique, but observed differences were generally significant (p < 0.001). For oxides, aerodynamic cluster size will dictate deposition in the lung, but primary particle size may influence biological activity. The GM diameter of alloy particles determined using PCM became smaller with decreasing aerodynamic size fraction; however, when suspended in liquid for CCSEM and LPC analyses, GM particle size decreased by a factor of two (p < 0.001) suggesting that alloy particles detach in liquid. Detachment of particles in liquid could have significance for the expected versus actual size (and number) distribution of aerosol delivered to an exposure subject. Thus, a suite of complimentary analytical techniques may be necessary for estimating size distribution. Consideration should be given to thoroughly understanding the influence of any liquid vehicle which may alter the expected aerosol size distribution

Inter-laminar shear stress in hybrid CFRP/austenitic steel

Bolted joints are the most common solution for joining composite components in aerospace structures. Critical structures such as wing to fuselage joints, or flight control surface fittings use bolted joining techniques. Recent research concluded that higher bearing strengths in composite bolted joints can be achieved by a CFRP/ Titanium hybrid lay-up in the vicinity of the bolted joint. The high costs of titanium motivate a similar research with the more cost competitive austenitic steel. An experimental program was performed in order to compare the apparent inter-laminar shear stress (ILSS) of a CFRP reference beam with the ILSS of hybrid CFRP/Steel beams utilizing different surface treatments in the metallic ply. The apparent ILSS was determined by short beam test, a three-point bending test. Finite element models using cohesive elements in the CFRP/Steel interface were built to simulate the short beam test in the reference beam and in the highest interlaminar shear stress hybrid beam. The main parameters for a FEM simulation of inter laminar shear are the cohesive elements damage model and appropriate value for the critical energy release rate. The results show that hybrid CFRP/Steel have a maximum ILSS very similar to the ILSS of the reference beam. Hybrid CFRP/Steel is a competitive solution when compared with the reference beam ILSS. FEM models were able to predict the maximum ILSS in each type of beam