Search

The compound 4-thioureidoiminomethylpyridinium perchlorate (perchlozone © ) is a novel anti-tuberculosis drug that is active in multiple drug resistance cases, but the compound is hepatotoxic. To decrease the systemic load and to achieve targeting, we encapsulated the drug into poly(lactic acid)-based micro- (1100 nm) and nanoparticles (170 nm) that were modified with single-chain camel immunoglobulin G (IgG) for targeting. Both micro- and nanoparticles formed stable suspensions in saline solution at particle concentrations of 10⁻50 mg/mL. The formulations were injected intraperitoneally and intravenously into the mice with experimental tuberculosis. The survival of control animals was compared to that of mice which were treated with daily oral drug solution, single intraperitoneal administration of drug-loaded particles, and those treated both intravenously and intraperitoneally by drug-loaded particles modified with polyclonal camel IgGs. The distribution of particles in the organs of mice was analyzed with immunofluorescence and liquid chromatography/mass spectrometry. Morphological changes related to tuberculosis and drug toxicity were registered. Phagocytic macrophages internalized particles and transported them to the foci of tuberculosis in inner organs. Nanoparticle-based drug formulations, especially those with IgG, resulted in better survival and lower degree of lung manifestations than the other modes of treatment., Competing Interests: The authors declare no conflicts of interest regarding this research.

Within the general nitrofuran carboxamide chemotype, chimera derivatives incorporating diversely substituted imidazoles attached via an alkylamino linker were synthesized. Antimycobacterial evaluation against drug-sensitive M. tuberculosis H37Rv strain identified five active druglike compounds which were further profiled against patient-derived M. tuberculosis strains in vitro. One of the compounds displayed promising potent activity (MIC 0.8 μg/mL) against one of such strains otherwise resistant to such first- and second-line TB therapies as streptomycin, isoniazid, rifampicin, ethambutol, kanamycin, ethionamide, capreomycin and amikacin. The compound was shown to possess low toxicity for mice (LD 50  = 900.0 ± 83.96 mg/kg) and to be similarly efficacious to etambutol, in the mouse model of drug-sensitive tuberculosis, and to neurotoxic cycloserine in mice infected with MDR tuberculosis., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Totally implanted venous access port (TIVAP) systems provide adequate quality of care and life, especially for oncology patients. Long-term vascular access is very important and easy to perform, but in some clinical situations, if patients have a superior caval system occlusion, femoral insertion may be the only option. We present a case of a 70-year-old colorectal adenocarcinoma patient diagnosed with subclavian vein hypoplasia. Her care team decided intraoperatively to implant a port system by the right femoral access. The patient was included in an active surveillance program with regular follow-ups and has had no complications by the end of 2017. This uncommon surgical approach provided this cancer patient with an opportunity to realize a chemotherapy program with optimal quality of life., Competing Interests: The authors have declared that no competing interests exist.

Whole-genome analysis of Mycobacterium tuberculosis isolates collected in Russia (N = 71) from patients with tuberculous spondylitis supports a detailed characterization of pathogen strain distributions and drug resistance phenotype, plus distinguished occurrence and association of known resistance mutations. We identify known and novel genome determinants related to bacterial virulence, pathogenicity, and drug resistance.

Background: During the period from 1996 to 2016, we have performed 281 thymectomies in patients with various diseases of the thymus. In 179 patients, thymic pathology was associated with autoimmune myasthenia gravis (MG), and, in 108 patients, thymoma was diagnosed., Methods: The majority of surgeries [254] were performed using video thoracoscopy, 79 of them with an additional cervical approach. The long-term results of video thoracoscopic thymectomies in myasthenic patients were followed up for 1 to 15.5 years., Results: In 26% of the patients, a complete and stable remission was achieved, in 47%-clinical manifestation improved. Local recurrence of thymoma developed in one patient (0.9%)., Conclusions: Comparison of postoperative complications and long-term results demonstrated that extended video-assisted thoracoscopic thymectomy (VATS-TE) is a radical, efficient, safe, technically feasible and a well-tolerated surgery. It improves the course of MG as a part of multimodality treatment more efficiently than a conservative therapy alone. The course of MG after VATS-TE shows that the cumulative incidence of remissions/improvements reaches its maximum by the 3rd year after the surgery. VATS-TE is radical and safe for removal of noninvasive thymomas up to 8 cm in size. Additional neck incision (VATS-TE + cervical approach) does not provide further advantages, but rather may be a cause of specific postoperative complications., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Vitamin D insufficiency is associated with autoimmune and chronic inflammatory diseases such as tuberculosis and sarcoidosis., Objectives: To evaluate the vitamin D-dependent mechanisms of immunity and autoimmunity in different forms of pulmonary tuberculosis and sarcoidosis., Methods: We measured the serum levels of 25(OH)D and 1,25(OH)2D, individual autoimmune profiles, plasma concentrations of cathelicidin, several hormones, and production of nine cytokines in patients with short- and long-duration tuberculosis and sarcoidosis., Results: The level of 25(OH)D was significantly decreased in all patients. Concentration of 1,25(OH)2D was elevated only in sarcoidosis, prolactin content was augmented only in tuberculosis. We saw no expected increase of cathelicidin levels in tuberculosis and sarcoidosis. The individual mean immune reactivity levels of autoantibodies to 24 antigens were significantly lower in tuberculosis and sarcoidosis patients compared to healthy controls. Pronounced deviations from individual mean immune reactivity levels were found for several autoantigens in all patients. The induced production of interferon gamma-γ, interleukin (IL) 2, 17, and 8 by peripheral blood mononuclear cells was significantly increased in patients of both tuberculosis groups, but spontaneous production of tumor necrosis factor-α, IL-2, and IL-6 was lower in the tuberculosis patients than in healthy controls. We registered marked differences in the groups of tuberculosis patients., Conclusions: We demonstrated the role of vitamin D deficiency in poor cathelicidin response in  tuberculosis and sarcoidosis. Both diseases are accompanied by significant changes in the autoimmune profile, probably related to the status of vitamin D and cytokine regulation.

Beijing B0/W148, a "successful" clone of Mycobacterium tuberculosis, is widespread in the Russian Federation and some countries of the former Soviet Union. Here, we used label-free gel-LC-MS/MS shotgun proteomics to discover features of Beijing B0/W148 strains that could explain their success. Qualitative and quantitative proteome analyses of Beijing B0/W148 strains allowed us to identify 1,868 proteins, including 266 that were differentially abundant compared with the control strain H37Rv. To predict the biological effects of the observed differences in protein abundances, we performed Gene Ontology analysis together with analysis of protein-DNA interactions using a gene regulatory network. Our results demonstrate that Beijing B0/W148 strains have increased levels of enzymes responsible for long-chain fatty acid biosynthesis, along with a coincident decrease in the abundance of proteins responsible for their degradation. Together with high levels of HsaA (Rv3570c) protein, involved in steroid degradation, these findings provide a possible explanation for the increased transmissibility of Beijing B0/W148 strains and their survival in host macrophages. Among other, we confirmed a very low level of the SseA (Rv3283) protein in Beijing B0/W148 characteristic for all «modern» Beijing strains, which could lead to increased DNA oxidative damage, accumulation of mutations, and potentially facilitate the development of drug resistance.