Hypomethylating Agents in Treatment of Myelodysplastic Syndrome

Thelkey to the successful treatment of myelodysplastic syndrome is the careful characterization and diagnosis of the disease, which includes clinical, cytogenetic, biological and molecular investigation of individual patients. Today therapeutic approaches to the treatment of such patients are differentiated and depend, first of all, on the subtype of the disease, age, general condition of the patients and the possibility of allogeneic hematopoietic cell transplantation. For young patients, the best option is transplantation, whereas in older patients, the standard of therapy is the use of hypomethylating agents (azacitidine, decitabine). These drugs promote hematologic improvement, elimination of transfusion dependence and prolongation of the duration of both general and leukemia free survival in elderly patients with concomitant pathology.Despite the fact that therapy with hypomethylating drugs is widely used and has good results, many respondents are losing their response within 1–2 years. Reasons for the development of resistance to this type of treatment are still unclear, and the insensitivity to drugs is associated with very poor prognosis in patients with all subtypes of myelodysplastic syndrome. Such data and the presence of numerous genetic and epigenetic mechanisms for the development of this pathology have prompted the use of combinations of drugs with different application points and are relevant in terms of research. In the literature review, the results of clinical studies on the use of hypomethylating agents in patients with MDS of low and high risk, as in monotherapy and combined schemes are presented.The nearest prospect of treatment of myelodysplastic syndrome is the creation of new treatment regimens based on a combination of drugs of different pathogenetic direction for the elimination of the dysplastic clone in order to achieve not only long-term remissions, but also lengthening the duration of overall survival, especially for patients with high risk myelodysplastic syndrome

A simulation of the cluster structures in Ge-Se vitreous chalcogenide semiconductors

A structure of germanium selenide glasses is simulated by the featured clusters built from the tetrahedral GeSe4 units up to the clusters with six germanium atoms (Ge6Se16H4 and Ge6Se16H8). Quantum chemical calculations at the DFT level with effective core potentials for Ge and Se atoms for the clusters of different composition reveal their relative stability and optical properties.Comment: 5 pages, 3 Figures include

Optimization of quantum cascade laser operation by geometric design of cascade active band in open and closed models

Using the effective mass and rectangular potential approximations, the theory of electron dynamic conductivity is developed for the plane multilayer resonance tunnel structure placed into a constant electric field within the model of open nanosystem, and oscillator forces of quantum transitions within the model of closed nanosystem. For the experimentally produced quantum cascade laser with four-barrier active band of separate cascade, it is proven that just the theory of dynamic conductivity in the model of open cascade most adequately describes the radiation of high frequency electromagnetic field while the electrons transport through the resonance tunnel structure driven by a constant electric field.Comment: 10 pages, 2 figure

Nematocidial activity of aqueous solutions of plants of the families Cupressaceae, Rosaceae, Asteraceae, Fabaceae, Cannabaceae and Apiaceae

In natural ecosystems of animals, introduction of larvae of parasitic nematodes into the litter layer from excrement facilitates their migration and search of new host vertebrate animals. In such conditions they are constantly affected by biologically active substances of the abundant species of plants which grow in pastures. Currently, the influence of substances present in the above-ground part of plants on the vitality of larvae of helminths in the environment remains unstudied. In this article, we present the results of our research on the nematocidial activity in vitro in the aqueous solutions of 21 species of plants distributed in the territory of Steppe Ukraine: Sanguisorba officinalis L., Rosa canina L., Crataegus sanguinea Pall., Crataegus pentagyna Waldst. & Kit. ex Willd., Armeniaca vulgaris Lam., Taraxacum officinale F. H. Wigg., Iva xanthiifolia Nutt., Artemisia campestris L., Arctium minus (Hill) Bernh., Ambrosia artemisiifolia L., Cannabis sativa L., Humulus lupulus L., Melilotus officinalis (L.) Pall., Vicia cracca L., Lotus ucrainicus Klok., Onobrychis arenaria (Kit.) DC., Foeniculum vulgare Mill., Eryngium planum L., Conium maculatum L., Juniperus communis L., Thuja occidentalis L. The level of vitality of nematode larvae of the Strongylida (Haemonchus contortus (Rudolphi, 1803)) and Rhabditida (Strongyloides papillosus (Wedl, 1856)) orders varied depending on the species of plant, and also five experimental concentrations in aqueous solutions tested in seven replications. The most notable nematocidial effect was exerted by Taraxacum officinale F. H. Wigg. – we observed death of larvae of third stage development L3 H. contortus and larvae of first-third stages L1–3 S. papillosus at 24 h exposure to 3% aqueous solution. Three percent aqueous solutions of S. officinalis and A. artemisiifolia displayed nematocidial properties only against S. papillosus: death of L1–3 S. papillosus was observed. Aqueous solutions of R. canina, A. vulgaris, A. minus, H. lupulus, V. cracca, L. ucrainicus, O. arenaria, E. planum, C. maculatum, J. communis, Th. occidentalis had lethal effect only on non-invasive larvae (larvae of the first and second stage L1–2) of S. papillosus. They displayed no nematocidial properties towards invasive larvae of H. contortus and S. papillosus. At exposure to aqueous solutions of the rest of the studied species of plants, over 50% of L3 H. contortus and L1–3 S. papillosus larvae remained alive. The determined patterns allow us to state that while living in the litter and soil in the root zone of plants nematode larvae undergoa negative influence caused by some plant species

Nematicidal activity of aqueous tinctures of medicinal plants against larvae of the nematodes Strongyloides papillosus and Haemonchus contortus

The study focuses on in vitro effect of aqueous tinctures of 48 species of herbaceous, shrub and tree plants on the first-third stage larvae of Strongyloides papillosus (Wedl, 1856) and third-stage larvae of Haemonchus contortus (Rudolphi, 1803) Cobb, 1898. The highest level of the effect was exerted by 3% aqueous tinctures of Wisteria sinensis (Sims) DC., Ailanthus altissima (Mill.) Swingle, Laburnum anagyroides Medik., Quercus petraea subsp. iberica (Steven ex M. Bieb.) Krassiln., Ginkgo biloba L., Colchicum autumnale L., Aristolochia manshuriensis Kom., Celastrus scandens L., Securigera varia (L.) Lassen, Magnolia kobus DC. Over 90% of the first and second non-invasive stage larvae of S. papillosus died at contact with these tinctures. The lowest parameters of LD50 were seen for L. anagyroides, Juniperus sabina L., C. scandens, M. kobus, A. manshuriensis, Wisteria sinensis (Sims) DC. and Securigera varia (L.) Lassen. Invasive larvae of S. papillosus and H. contortus were resistant to the effect of all the 48 surveyed species of plants. Third-stage larvae of H. contortus remained vital when exposed for 24 h to all the studied concentrations up to 3% aqueous tincture of plants. The results of the experiments and also the analysis of the literature indicate the necessity to continue the survey on nematocidial activity of aqueous tinctures and alcveshol extracts of plants