Fullerene C60 Conjugate with Folic Acid and Polyvinylpyrrolidone for Targeted Delivery to Tumor Cells.

The use of targeted drug delivery systems, including those based on selective absorption by certain receptors on the surface of the target cell, can lead to a decrease in the minimum effective dose and the accompanying toxicity of the drug, as well as an increase in therapeutic efficacy. A fullerene C60 conjugate (FA-PVP-C60) with polyvinylpyrrolidone (PVP) as a biocompatible spacer and folic acid (FA) as a targeting ligand for tumor cells with increased expression of folate receptors (FR) was obtained. Using 13C NMR spectroscopy, FT-IR, UV-Vis spectrometry, fluorometry and thermal analysis, the formation of the conjugate was confirmed and the nature of the binding of its components was established. The average particle sizes of the conjugate in aqueous solutions and cell culture medium were determined using dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). The FA-PVP-C60 showed antiradical activity against •DPPH, •OH and O2•-, but at the same time, it was shown to generate 1O2. It was found that the conjugate in the studied concentration range (up to 200 µg/mL) is non-toxic in vitro and does not affect the cell cycle. To confirm the ability of the conjugate to selectively accumulate through folate-mediated endocytosis, its uptake into cells was analyzed by flow cytometry and confocal microscopy. It was shown that the conjugate is less absorbed by A549 cells with low FR expression than by HeLa, which has a high level of expression of this receptor.

Philadelphia-positive case negative for JAK2 V617F mutation with hyperdiploidic karyotype: A case report.

Chronic myeloid leukemia (CML) is one of the most common hematological malignancies and accounts for 15-20% of all leukemia cases. The cytogenetic marker of CML is the presence of Philadelphia chromosome (Ph) in >95% of patients. The current case reports a 83-year old woman who was directed to the genetic laboratory for a cytogenetic and molecular-genetic analysis suspected to be Ph positive [(+)]. Karyotype analysis of a bone marrow sample revealed a hyperdiploid karyotype in a part of Ph (+) cells with additional chromosomes 8, 10 and 12. Restriction analysis for V617F JAK2 mutation was negative, while the quantitative RT-qPCR assay indicated BCR-ABL/ABL transcript at the level of 120% International Scale (IS). Generally cytogenetic complexities are important in the prognostic evaluation of CML. Besides the Ph chromosome, a variet of chromosomal aberrations may be associated with CML. A total of 5-10% of these cases show complex translocations involving another chromosome. The current case is Ph(+) demonstrating an additional hyperdiploid karyotype clone with three additional autosomes (8, 10 and 12). This case highlights the significance of cytogenetic abnormalities on the prognosis of CML.

Effectiveness of a fixed anterior bite plane in Class II deep-bite patients.

Orthodontic treatment of patients with distoclusion combined with dental deep bite and linguo version of the front upper teeth is one of the most difficult forms of malocclusion to treat to a functional and morphological optimum. Our objective was to analyze the efficacy of a fixed anterior bite plane appliance to disclude the teeth and correct this type of malocclusion. At the Department of Orthodontics MSUMD (Moscow State University of Medicine and Dentistry), we proposed the use of a fixed anterior bite plane for the effective treatment of patients with distoclusion combined to a dental deep bite. This appliance was used in 35 patients aged 11 to 15 years (13.2 +/- 1.2) with distoclusion combined with deep bite in a therapeutical approach that also involved an osteopathic correction. The appliance permitted the correction of the distoclusion by discluding the posterior teeth, allowing eruption of the molars and premolars which improved the occlusal plane line (Curve of Spee) and changed the inclination of the upper incisors which liberated the mandible from its retruded position. We also noted an effect on the postural status of the patient.