SYNTHESIS AND ANTI-TRICHINELLA SPIRALIS ACTIVITY IN VITRO OF SOME NEW 1H-BENZIMIDAZOLES

Novel derivatives of 1H-benzimidazole which combine into a single molecule two pharmacophores – the benzimidazole and piperazine rings possessing antihelmintic activity have been synthesized. Their structures were confirmed by IR, 1H NMR, 13C NMR and elemental analysis techniques.The compounds exhibited remarkable effect on the viability of isolated Trichinella spiralis muscle larvae in in vitro model at a dose of 100 μg/ml after 24 h. The results obtained by the hepatotoxicity test showed that compound 4 had the lowest hepatotoxity.Novel derivatives of 1H-benzimidazole which combine into a single molecule two pharmacophores – the benzimidazole and piperazine rings possessing antihelmintic activity have been synthesized. Their structures were confirmed by IR, 1H NMR, 13C NMR and elemental analysis techniques.The compounds exhibited remarkable effect on the viability of isolated Trichinella spiralis muscle larvae in in vitro model at a dose of 100 μg/ml after 24 h. The results obtained by the hepatotoxicity test showed that compound 4 had the lowest hepatotoxity

Tomosyn inhibits synaptic vesicle priming in Caenorhabditis elegans

Caenorhabditis elegans TOM-1 is orthologous to vertebrate tomosyn, a cytosolic syntaxin-binding protein implicated in the modulation of both constitutive and regulated exocytosis. To investigate how TOM-1 regulates exocytosis of synaptic vesicles in vivo, we analyzed C. elegans tom-1 mutants. Our electrophysiological analysis indicates that evoked postsynaptic responses at tom-1 mutant synapses are prolonged leading to a two-fold increase in total charge transfer. The enhanced response in tom-1 mutants is not associated with any detectable changes in postsynaptic response kinetics, neuronal outgrowth, or synaptogenesis. However, at the ultrastructural level, we observe a concomitant increase in the number of plasma membrane-contacting vesicles in tom-1 mutant synapses, a phenotype reversed by neuronal expression of TOM-1. Priming defective unc-13 mutants show a dramatic reduction in plasma membrane-contacting vesicles, suggesting these vesicles largely represent the primed vesicle pool at the C. elegans neuromuscular junction. Consistent with this conclusion, hyperosmotic responses in tom-1 mutants are enhanced, indicating the primed vesicle pool is enhanced. Furthermore, the synaptic defects of unc-13 mutants are partially suppressed in tom-1 unc-13 double mutants. These data indicate that in the intact nervous system, TOM-1 negatively regulates synaptic vesicle priming. © 2006 Gracheva et al

Modified Desolvation Method Enables Simple One-Step Synthesis of Gelatin Nanoparticles from Different Gelatin Types with Any Bloom Values

Gelatin nanoparticles found numerous applications in drug delivery, bioimaging, immunotherapy, and vaccine development as well as in biotechnology and food science. Synthesis of gelatin nanoparticles is usually made by a two-step desolvation method, which, despite providing stable and homogeneous nanoparticles, has many limitations, namely complex procedure, low yields, and poor reproducibility of the first desolvation step. Herein, we present a modified one-step desolvation method, which enables the quick, simple, and reproducible synthesis of gelatin nanoparticles. Using the proposed method one can prepare gelatin nanoparticles from any type of gelatin with any bloom number, even with the lowest ones, which remains unattainable for the traditional two-step technique. The method relies on quick one-time addition of poor solvent (preferably isopropyl alcohol) to gelatin solution in the absence of stirring. We applied the modified desolvation method to synthesize nanoparticles from porcine, bovine, and fish gelatin with bloom values from 62 to 225 on the hundreds-of-milligram scale. Synthesized nanoparticles had average diameters between 130 and 190 nm and narrow size distribution. Yields of synthesis were 62–82% and can be further increased. Gelatin nanoparticles have good colloidal stability and withstand autoclaving. Moreover, they were non-toxic to human immune cells. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Funding: The reported study was funded by RFBR and Kaliningrad Oblast according to the research project № 19-415-393005 (preparation of fluorescence gelatin nanoparticles and study of their fluorescent properties), by RFBR research project 19-015-00408 (preparation of gelatin nanoparticles by the desolvation method), and by Ministry of Science and Higher Education of the Russian Federation within the framework of the Russian State Assignment under contract No. AAAA-А19-119112290010-7 (assessment of nanoparticles cytotoxicity)

Study of the effectiveness of supplementary feeding in patients with inherited enzyme deficiency

The successful provision of optimal nutrition in children with serious diseases depends on the right diet, as well as the addition of specialized mixtures for its correction. The aim of the study was to study the effectiveness of supplemental nutrition in hereditary fermentopathy (cystic fibrosis) in children. The work included a three-year follow-up of 69 children aged 3 to 15 years suffering from cystic fibrosis. Patients were divided into two groups: 37 patients with cystic fibrosis group 1, receiving a modified version of treatment with additional enteral nutrition and 32 patients with cystic fibrosis group 2, receiving traditional treatment. The study conducted a comparative analysis of changes in trophic status in patients using nutritional support mixture produced in the Russian Federation – "Nutrien-standard"in diet therapy. Laboratory, functional and anthropometric parameters were monitored once a month. A significant increase in the physical development of patients was obtained only in the second year of use in the diet of supplementary nutrition, p<0.05. At the 3rd year of treatment, the results of positive dynamics of nutritional status in both groups were confirmed, while the increase in body mass index in the main group was 6.7%, and in the control group-only 1% (p<0.05). It is noted that the use of this mixture allows to achieve positive dynamics of nutritional status in 27% of patients and in 73% of cases to completely eliminate it. The obtained results prove the expediency of additional use of "Nutrient-standard" mixture in the complex therapy of patients with hereditary pancreatic enzyme deficiency, cystic fibrosi

Ruthenium(II)–arene and triruthenium-carbonyl cluster complexes with new water-soluble phopsphites based on glucose: Synthesis, characterization and antiproliferative activity

New water-soluble 3,5,6-bicyclophosphite ligands based on glucose modified with uracil, 5-fluorouracil or thymine are reported. The phosphite ligands were subsequently reacted with bis[dichlorido(η6-p-cymene)ruthenium(II)] and trirutheniumdodecacarbonyl to afford monoruthenium analogues of RAPTA-C and triruthenium clusters with 1–3 phosphite ligands, respectively. The influence of ligands on the stability of the compounds and the antiproliferative activity of the compounds was investigated

ANTI-FOGGING COATINGS FOR MEDICAL DEVICE APPLICATION

Anti-fogging coatings are widely used in industry, including medical device manufacturing. Potential application of superhydrophobic and superhydrophilic surfaces for manufacturing of airway adapter of mainstream capnometer had been studied

FIBROSCLEROSIS AND SCLEROSING ADENOSIS WITH MICROCALCIFICATIONS IN THE BREAST. MOLECULAR PATHOGENESIS, TIMELY DIAGNOSIS AND TREATMENT

A brief review of current data on the generality of the epidemiology and molecular pathogenesis of breast cancer and benign breast diseases is presented. Currently, a type of mastopathy, fibrosclerosis/sclerosing adenosis, ac­companied by the formation of microcalcifications, is considered as a benign pathological condition with a high risk of malignancy, and also as a pre-start condition of a possible transition of mastopathy to cancer. In the review is discussed the fundamental biological process of the epithelial-mesenchymal transition (EMT) as a molecular pathogenetic basis of this phenomenon. Identification of the above mentioned pathological changes using mam­mography and refined diagnostics using a vacuum aspiration biopsy allow timely treatment of fibrosclerosis and sclerosing adenosis with Indinol® Forto, a drug of pathogenetic action based on indole-3-carbinol, due to its mul­tiple anticancer and oncoprophylactic activity, including ability to reverse at the epigenetic level the EMT process abnormally proceeding in these benign breast diseases