Ellagic Acid Derivatives from Rubus ulmifolius Inhibit Staphylococcus aureus Biofilm Formation and Improve Response to Antibiotics

Biofilms contribute to the pathogenesis of many forms of Staphylococcus aureus infection. Treatment of these infections is complicated by intrinsic resistance to conventional antibiotics, thus creating an urgent need for strategies that can be used for the prevention and treatment of biofilm-associated infections.This study demonstrates that a botanical natural product composition (220D-F2) rich in ellagic acid and its derivatives can limit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility. The source of this composition is Rubus ulmifolius Schott. (Rosaceae), a plant used in complementary and alternative medicine in southern Italy for the treatment of skin and soft tissue infections. All S. aureus clonal lineages tested exhibited a reduced capacity to form a biofilm at 220D-F2 concentrations ranging from 50-200 µg/mL, which were well below the concentrations required to limit bacterial growth (530-1040 µg/mL). This limitation was therapeutically relevant in that inclusion of 220D-F2 resulted in enhanced susceptibility to the functionally-distinct antibiotics daptomycin, clindamycin and oxacillin. Testing with kidney and liver cell lines also demonstrated a lack of host cell cytotoxicity at concentrations of 220D-F2 required to achieve these effects.These results demonstrate that extract 220D-F2 from the root of Rubus ulmifolius can be used to inhibit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility without toxic effects on normal mammalian cells. Hence, 220D-F2 is a strong candidate for development as a botanical drug for use in the prevention and treatment of S. aureus biofilm-associated infections

Re-modeling ELISA kits embedded in an automated system suitable for on-line detection of algal toxins in seawater

The increasing demand by citizens and environmental organization for the protection, preservation, and possible restoration of the marine environment has made seawater protection one of the urgent priorities of the European Union. In this contest, extensive monitoring and surveillance are required to correctly assess the current status of marine environment, paying attention not only to traditional chemical parameters, but also to the so-called “emerging pollutants”. Among these, marine biotoxins represent a serious hazard, because they can accumulate in fish and mussels and enter the food chain. The detection of marine toxins released by algae has mostly been directed on the analysis of fish/shellfish homogenate rather than seawater samples. To fill this gap, in this work, we propose the re-modeling of ELISA kits to set-up non-automated direct competitive ELIMC (Enzyme-Linked Immuno-Magnetic Colorimetric) assays for the detection of Domoic Acid (DA), Okadaic Acid (OA) and Saxitoxin (STX) in seawater. For each toxin, linear working range, sensitivity and detection limit (0.03, 0.05, 0.01 ng/mL for DA, OA and STX, respectively) of the ELIMC assays were calculated. After evaluation of seawater matrix effect and recovery study, ELIMC assays were integrated within a novel automated networked system (ASMAT - Analytical System for Marine Algal Toxins) based on the micro Loop Flow Reactor (μLFR) technology, suitable for on-line monitoring of marine toxins. Once established the best operational conditions, ASMAT was calibrated towards DA, OA and STX verifying its capability to detect sub-ppb levels of the target toxins. Analysis of DA, OA and STX in real samples of marine water, sampled in Alonnisos (Greece) were carried out in laboratory using ELIMC assays, ASMAT and ELISA Kits, for a comparative evaluation. Finally, on-line suitability of ASMAT as an early warning alarm system was demonstrated by a field installation within a floating platform in the port of La Spezia (Italy)

Chronic inflammation in multiple sclerosis — seeing what was always there

Activation of innate immune cells and other brain compartmentalized inflammatory cellsin the brains and spinal cords of people with relapsing–remitting multiple sclerosis (MS) and progressive MS have been well described histopathologically. However, conventional clinical MRI is largely insensitive to this inflammatory activity. The past two decades have seen the introduction of quantitative dynamic MRI scanning with contrast agents that are sensitive to the reduction in blood–brain barrier integrity associated with inflammation and to the trafficking of inflammatory myeloid cells. New MRI imaging sequences provide improved contrast for better detection of grey matter lesions. Quantitative lesion volume measures and magnetic resonance susceptibility imaging are sensitive to the activity of macrophages in the rims of white matter lesions. PET and magnetic resonance spectroscopy methods also can be used to detect contributions from innate immune activation in the brain and spinal cord. Some of these advanced research imaging methods for visualization of chronic inflammation are practical for relatively routine clinical applications. Observations using these techniques suggest ways of stratifying patients with MS to improve their care. The imaging methods also provide new tools to support the development of therapies for chronic inflammation in MS