Update on acute disseminated encephalomyelitis in children and adolescents

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated, inflammatory demyelinating disease of the central nervous system (CNS) that usually affects children and young adults after an infection or vaccination. The presence of several conditions mimicking ADEM, added to the lack of specific biomarkers, makes diagnosis potentially hard. Prompt diagnosis is necessary to start adequate treatment to improve the clinical course and long-term outcome. Because of its heterogeneity in both clinical presentation and course, challenges remain in establishing the most appropriate therapeutic approach in each patient. The aim of this review is to provide an update on management of this disease with a focus on acute treatment and to give suggestions for future research. We showed that there are currently no guidelines that help clinicians manage ADEM and therapeutic decisions are often made on a case-by-case basis. Further studies are necessary to identify clinical, laboratory, and instrumental criteria that could be correlated with outcomes and guide clinicians in choosing when and what treatment should be given in each case

Herbicidal potential of ophiobolins produced by Drechslera gigantea

Drechslera gigantea, a potential mycoherbicide of grass weeds, was isolated in Florida from naturally infected large crabgrass (Digitaria sanguinalis); it produces phytotoxic metabolites in liquid culture. The main metabolite was identified by spectroscopic methods and optical properties as ophiobolin A (1), a well-known phytotoxic sesterterpene produced by several phytopathogenic fungi of important crops and already extensively studied for its interesting biological activities. The other three minor metabolites proved to be related to ophiobolin A and were identified using the same techniques as 6-epi-ophiobolin A and 3-anhydro-6-epi-ophiobolin A (2 and 3) and ophiobolin I (4). Assayed on punctured detached leaves of several grass and dicotyledon weeds, ophiobolin A proved to be on average more phytotoxic as compared to the other related compounds. Some structural features appear to be important for the phytoxicity, such as the hydroxy group at C-3, the stereochemistry at C-6, and the aldehyde group at C-7. Furthermore, grass weeds usually proved to be more sensitive to the phytotoxins than dicotyledons, on which ophiobolin A caused the appearance of large necrosis even at the lowest concentration assayed. This is the first report about the production of ophiobolins from D. gigantea and of the proposed use as potential natural herbicides against grass weeds. © 2006 American Chemical Society

Ophiobolin E and 8-epi-ophiobolin J produced by Drechslera gigantea, a potential mycoherbicide of weedy grasses

Drechslera gigantea, a fungal pathogen isolated from large crabgrass (Digitaria sanguinalis) and proposed as a potential mycoherbicide of grass weeds, produces phytotoxic metabolites in liquid and solid cultures. Ophiobolin A and three minor ophiobolins i.e., 6-epi-ophiobolin A, 3-anhydro-6-epi-ophiobolin A and ophiobolin I were obtained from the liquid culture broths. Interestingly and unexpectedly, ophiobolins also appeared in cultures of this fungus and they were isolated together with the known ophiobolins B and J, and designed as ophiobolin E and 8-epi-ophiobolin J. They were characterized using essentially spectroscopic methods. It is noteworthy that D. gigantea produces such a plethora of bioactive organic substances. Some structure-activity relationship results are also discussed in this report. © 2006 Elsevier Ltd. All rights reserved

Drazepinone, a trisubstituted tetrahydronaphthofuroazepinone with herbicidal activity produced by Drechslera siccans

When grown in a minimal-defined medium, a strain of Drechslera siccans, a pathogenic fungus isolated from seeds of Lolium perenne, produced phytotoxic metabolites. This strain is one of the best toxin producers among several grass pathogenic fungal strains collected and tested to find phytotoxins to be used as natural herbicides of monocot weeds. From the culture filtrates of D. siccans, we isolated a new phytotoxic trisubstituted naphthofuroazepinone, named drazepinone, and characterised it as a 3,5,12a-trimethyl-2,5,5a,12a-tetrahydro- 1H-naphtho[2′,3′:4,5]furo[2,3-b]azepin-2-one. Assayed at 2 μg μl-1 solution the novel metabolite proved to have broad-spectrum herbicidal properties, without antibacterial and antifungal activities, and low zootoxic activity. Its original chemical structure and the interesting biological properties make drazepinone a potential natural herbicide. © 2005 Elsevier Ltd. All rights reserved

Investigation into the effects of high-Z nano materials in proton therapy

High-Z nano materials have been previously shown to increase the amount of dose deposition within the tumour due to an increase in secondary electrons. This study evaluates the effects of high-Z nano materials in combination with protons, and the impact of proton energy, nanoparticle material and concentration. These effects were studied in silico through Monte Carlo simulation and experimentally through a phantom study, with particular attention to macroscale changes to the Bragg peak in the presence of nanoparticles. Three nanoparticle materials were simulated (gold, silver and platinum) at three concentrations (0.01, 0.1 and 6.5 mg ml(-1)) at two clinical proton energies (60 and 226 MeV). Simulations were verified experimentally using Gafchromic film measurements of gold nanoparticles suspended in water at two available high concentrations (5.5 mg ml(-1) and 1.1 mg ml(-1)). A significant change to Bragg peak features was evident, where at 226 MeV and 6.5 mg ml(-1), simulations of gold showed a 4.7 mm longitudinal shift of the distal edge and experimentally at 5.5 mg ml(-1), a shift of 2.2 mm. Simulations showed this effect to be material dependent, where platinum having the highest physical density caused the greatest shift with increasing concentration. A dose enhancement of 6%  ±  0.05 and 5%  ±  0.15 (60 MeV and 226 MeV, respectively) was evident with gold at 6.5 mg ml(-1) to water alone, compared to the 21%  ±  0.53 observed experimentally as dose to film with 5.5 mg ml(-1) of gold nanoparticles suspended in water at 226 MeV. The introduction of nanoparticles has strong potential to enhance dose in proton therapy, however the changes to the Bragg peak distribution that occur with high concentrations need to be accounted for to ensure tumour coverage

Anti-biofilm inhibitory synergistic effects of combinations of essential oils and antibiotics

In recent years, the increase of bacteria antibiotic-resistance has been a severe problem for public health. A useful solution could be to join some phytochemicals naturally present in essential oils (EOs) to the existing antibiotics, with the aim to increase their efficacy in therapies. According to in vitro studies, EOs and their components could show such effects. Among them, we studied the activity of Cinnammonum zeylanicum, Mentha piperita, Origanum vulgare, and Thymus vulgaris EOs on bacterial biofilm and their synergism when used in association with some common antibiotics such as norfloxacin, oxacillin, and gentamicin. The chemical composition of EOs was determined using gas chromatography (GC) coupled with mass spectrometry (MS) techniques. The EOs drug efficacy was evaluated on four different strains of Gram-positive bacteria forming biofilms. The synergistic effects were tested through the chequerboard microdilution method. The association EOs-antibiotics showed a strong destruction of the biofilm growth of the four bacterial species considered. The interaction of norfloxacin with EOs was the most effective in all the tested combinations against the strains object of this study. These preliminary results suggest the formulation of a new generation of antimicrobial agents based on a combination of antimicrobial compounds with different origin

Comparison between two treatment protocols with recombinant Human Erythropoietin (rHuEpo) in the treatment of late anemia in neonates with Rh-Isoimmunization

Objectve. The Rh-hemolytic disease can lead to a late anemia by hemolytic and hyporigenerative mechanism. We compared the effectiveness of rHuEPO in two care protocols that differ for doses of rHuEPO administrated and for timing of administration. Methods. A cohort of 14 neonates was investigated. The neonates were treated with two different protocols. Protocol A: a dose of 200 U/kg/day of rHuEpo administered subcutaneously starting from the end of the second week of life; Protocol B: a dose of 400 U/kg/day of rHuEpo administered subcutaneously starting from the end of the first week of life. Results. The hematocrit values in the protocol A group decreased during treatment (32,5% vs 25,2%), whereas the hematocrit value in protocol B group remained almost stable (38,7% vs 42,8%). The mean numbers of platelets remained stable in both groups while neutrophils increased in protocol A group and decreased in protocol B (p<0,05). Reticulocyte count increased during treatment in both groups, although only in protocol B group it was statistically significative (p<0,05). Conclusions. Our results suggest a similar efficacy between the two treatment protocols. Increasing doses of rHuEPO do not seem enhancing their effectiveness and the incidence of side effects

Mesenchymal Stem Cells in Myeloid Malignancies: A Focus on Immune Escaping and Therapeutic Implications

The importance of the bone marrow microenvironment forming the so-called niche in physiologic hemopoiesis is largely known, and recent evidences support the presence of stromal alterations from the molecular to the cytoarchitectural level in hematologic malignancies. Various alterations in cell adhesion, metabolism, cytokine signaling, autophagy, and methylation patterns of tumor-derived mesenchymal stem cells have been demonstrated, contributing to the genesis of a leukemic permissive niche. This niche allows both the ineffective haematopoiesis typical of myelodysplastic syndromes and the differentiation arrest, proliferation advantage, and clone selection which is the hallmark of acute myeloid leukemia. Furthermore, the immune system, both adaptive and innate, encompassing mesenchymal-derived cells, has been shown to take part to the leukemic niche. Here, we critically review the state of art about mesenchymal stem cell role in myelodysplastic syndromes and acute myeloid leukemia, focusing on immune escaping mechanisms as a target for available and future anticancer therapies

Biosensors in clinical practice : focus on oncohematology

Biosensors are devices that are capable of detecting specific biological analytes and converting their presence or concentration into some electrical, thermal, optical or other signal that can be easily analysed. The first biosensor was designed by Clark and Lyons in 1962 as a means of measuring glucose. Since then, much progress has been made and the applications of biosensors are today potentially boundless. This review is limited to their clinical applications, particularly in the field of oncohematology. Biosensors have recently been developed in order to improve the diagnosis and treatment of patients affected by hematological malignancies, such as the biosensor for assessing the in vitro pre-treatment efficacy of cytarabine in acute myeloid leukemia, and the fluorescence resonance energy transfer-based biosensor for assessing the efficacy of imatinib in chronic myeloid leukemia. The review also considers the challenges and future perspectives of biosensors in clinical practice