Olfactory transport efficiency of the manganese oxide nanoparticles (II) after their single or multiple intranasal administrations

In experiments with reusable inhalation of nano-sized metal oxide particles, it has been shown that there is no significant relationship between the number of presentations and the metal concentration in the olfactory bulb. This fact raises the question of a possible decrease in the efficiency of particulate capturing by the olfactory epithelium after their repeated application into the nasal cavity. In this study, we compared the effectiveness of nasal transport of paramagnetic nanoparticles after their single and multiple intranasal administration and evaluated their effects on the morphological and functional characteristics of the olfactory system. Based on the data, the accumulation of MnO-NPs in the olfactory bulb of mice was reduced after repeated intranasal application. In addition, the decrease in the efficiency of olfactory transport observed after repeated administration of MnO-NPs was partially restored by intranasal application of mucolytic (0.01 M N-acetyl-L-cysteine). In this case, the concentration of particles in the olfactory bulb was proportional to the volume of the structure, which in particular depends on the number of synaptic contacts between the mitral cell of the olfactory bulb (OB) and olfactory epithelium (OE). It should be noted that multiple intranasal injections of MnO-NPs reduce mouse OE thickness. Thus, repeated intranasal introduction of MnO-NPs reduces the efficiency of nanoparticle olfactory transport from the nasal cavity to the brain, which is combined with the increase in the viscosity of the mucosal layer and the reduction in the number of synaptic contacts between OB and OE. These results indicate the presence of the natural mechanisms of protection against the penetration of pathogens and xenobiotics into the olfactory epithelium; they also allow us to formulate practical recommendations on intranasal drugs delivery

Low-temperature properties of monoalcohol glasses and crystals

We review and jointly discuss both earlier and recent experiments conducted by us on simple aliphatic glass-forming monoalcohols at low temperatures, including specific heat, thermal conductivity, Brillouin scattering and x-ray diffraction experiments. The family of simple monoalcohols constitutes an interesting model system to explore different relevant issues concerning molecular glass-forming liquids, low-temperature universal proper-ties of glasses, and even the glass transition phenomenon itself. More specifically, we discuss the role played by the molecular aspect ratio in vitrification/crystallization kinetics, the reported appearance of particular cases of polymorphism (in ethanol) and polyamorphism (in butanol), and especially the influence of position isomerism and the location of the hydrogen bond on the lattice dynamics and hence on the low-temperature universal prop-erties of glasses

The effect of a single administration of streptozotocin on hippocampus metabolites in NODSCID mice

The significant increase in the number of people diagnosed with diabetes mellitus in recent years makes studies of this problem topical. The persistent hyperglycemia accompanying the development and course of type 1 diabetes mellitus (T1DM) can affect the func-tional and structural levels of the organization of the central nervous system. These changes may be medi­ated by metabolic aberrations. Magnetic resonance spectroscopy (MRS) is a common method of intravital detection of metabolic reactions. In this study, MRS of the hippocampus of NOD.CB17-Prkdcscid/NcrCrl mice (NODSCID) was performed 4 days after the administration of streptozotocin (STZ) to assess the effect of STZ itself, and 60 days after the administration of STZ to another group of animals to assess the effect of chronic hyperglycemia caused by the delayed ef­fect of STZ, involving the death of pancreatic β-cells. The simulation of T1DM by STZ administration is used worldwide. Nevertheless, the question remains whether there is a short-term effect of the introduc­tion of STZ at the level of hippocampal metabolites recorded by MRS. The comparison of experimental and control animal groups revealed no effect of STZ on metabolites in the hippocampus of NODSCID mice on day 4 after its administration. In contrast, another comparison of the experimental and control animals on day 60 after STZ administration showed elevated contents of alanine and taurine, and a reduced lactate content. Thus, the introduction of STZ itself does not affect the metabolism of the hippocampus, and MRS is a promising method for assessing the effect of T1DM on brain metabolism in animals

Low-temperature properties of monoalcohol glasses and crystals

We review and jointly discuss both earlier and recent experiments conducted by us on simple aliphatic glass-forming monoalcohols at low temperatures, including specific heat, thermal conductivity, Brillouin scattering and x-ray diffraction experiments. The family of simple monoalcohols constitutes an interesting model system to explore different relevant issues concerning molecular glass-forming liquids, low-temperature universal proper-ties of glasses, and even the glass transition phenomenon itself. More specifically, we discuss the role played by the molecular aspect ratio in vitrification/crystallization kinetics, the reported appearance of particular cases of polymorphism (in ethanol) and polyamorphism (in butanol), and especially the influence of position isomerism and the location of the hydrogen bond on the lattice dynamics and hence on the low-temperature universal prop-erties of glasses

The role of olfactory transport in the penetration of manganese oxide nanoparticles from blood into the brain

There is no doubt that various nanoparticles (NPs) can enter the brain from the nasal cavity. It is assumed that NPs can penetrate from blood into the central nervous system (CNS) only by breaking the blood–brain barrier (BBB). The accumulation of NPs in CNS can provoke many neurological diseases; therefore, the understanding of its mechanisms is of both academic and practical interest. Although hitting from the surface of the lungs into the bloodstream, NPs can accumulate in various mucous membranes, including the nasal mucosa. Thus, we cannot rule out the ability of NPs to be transported from the bloodstream to the brain through the olfactory uptake. To test this hypothesis, we used paramagnetic NPs of manganese oxide (Mn3O4-NPs), whose accumulation patterns in the mouse brain were recorded using T1-weighted magnetic resonance imaging. The effect of intranasal application of endocytosis and axonal transport inhibitors on the brain accumulation patterns of intranasally or intravenously injected Mn3O4-NPs was evaluated. A comparative analysis of the results showed that the transport of Mn3O4-NPs from the nasal cavity to the brain is more efficient than their local permeation through BBB into CNS from the bloodstream, for example with the accumulation of Mn3O4NPs in the dentate gyrus of the hippocampus, and through the capture and transport of NPs from the blood by olfactory epithelium cells. Also, experiments with the administration of chlorpromazine, a specific inhibitor of clathrin-dependent endocytosis, and methyl-β-cyclodextrin, inhibitor of the lipid rafts involved in the capture of substances by endothelium cells, showed differences in the mechanisms of NP uptake from the nasal cavity and from the bloodstream. In this study, we show a significant contribution of axonal transport to NP accumulation patterns in the brain, both from the nasal cavity and from the vascular bed. This explains the accumulation of different sorts of submicron particles (neurotropic viruses, insoluble xenobiotics, etc.), unable to pass BBB, in the brain. The results will add to the understanding of the pathogenesis of various neurodegenerative diseases and help studying the side effects of therapeutics administered intravenously

Olfactory transport efficiency of the amorphous and crystalline manganese oxide nanoparticles

The ability to deliver particulated xenobiotics and therapeutic drugs directly from the nasal cavity to the central nervous system, bypassing the hemato-encephalic barrier, determines a high importance of investigation of factors influencing this process. It was shown that the bioavailability of solid particles is influenced by their size and surface charge. At the same time, the impact of a crystal structure (crystalline/amorphous) has been poorly investigated. In this study, using sexually mature male C57BL/6J mice, we analyzed the efficiency of the nose-to-brain transport of crystalline and amorphous manganese oxide nanoparticles. T1-weighted magnetic resonance imaging (MRI) was used to evaluate the accumulation of manganese nanoparticles in olfactory bulb (OB) and olfactory epithelium (OE). So, it has been established that amorphous particles have higher accumulation rate in OE and OB in comparison with crystalline particles after their intranasal administration. The unequal ability of amorphous and crystalline particles to overcome the mucosal layer covering the OE may be one of the possible reasons for the different nose-to-brain transport efficiency of particulated matter. Indeed, the introduction of mucolytic (dithiothreitol) 20 minutes prior to intranasal particle application did not influence the accumulation of amorphous particles in OE and OB, but enhanced the efficiency of crystalline nanoparticle entry. Data on the different intake of amorphous and crystalline nanoparticles from the nasal cavity to the brain, as well as the evidence for the key role of the mucosal layer in differentiating the penetrating power of these particles will be useful in developing approaches to assessing air pollution and optimizing the methods of inhalation therapy

VARIANT OF DECODING OF RESULTS OF DILATOMETRIC MEASUREMENTS IN STEELS

A variant of decoding the results of dilatometric measurements in steels using as a „zero“ line the effect of thermal expansion of the sample material minus the dilatometric effects initiated by phase and structural transformations is proposed.Предложен вариант расшифровки результатов дилатометрических измерений в сталях с использованием в качестве «нулевой» линии эффекта теплового расширения материала образца за минусом дилатометрических эффектов, инициируемых фазовыми и структурными превращениями

Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase δ syndrome 2: A cohort study

Background Activated phosphoinositide 3-kinase δ syndrome (APDS) 2 (p110δ-activating mutations causing senescent T cells, lymphadenopathy, and immunodeficiency [PASLI]–R1), a recently described primary immunodeficiency, results from autosomal dominant mutations in PIK3R1, the gene encoding the regulatory subunit (p85α, p55α, and p50α) of class IA phosphoinositide 3-kinases. Objectives We sought to review the clinical, immunologic, and histopathologic phenotypes of APDS2 in a genetically defined international patient cohort. Methods The medical and biological records of 36 patients with genetically diagnosed APDS2 were collected and reviewed. Results Mutations within splice acceptor and donor sites of exon 11 of the PIK3R1 gene lead to APDS2. Recurrent upper respiratory tract infections (100%), pneumonitis (71%), and chronic lymphoproliferation (89%, including adenopathy [75%], splenomegaly [43%], and upper respiratory tract lymphoid hyperplasia [48%]) were the most common features. Growth retardation was frequently noticed (45%). Other complications were mild neurodevelopmental delay (31%); malignant diseases (28%), most of them being B-cell lymphomas; autoimmunity (17%); bronchiectasis (18%); and chronic diarrhea (24%). Decreased serum IgA and IgG levels (87%), increased IgM levels (58%), B-cell lymphopenia (88%) associated with an increased frequency of transitional B cells (93%), and decreased numbers of naive CD4 and naive CD8 cells but increased numbers of CD8 effector/memory T cells were predominant immunologic features. The majority of patients (89%) received immunoglobulin replacement; 3 patients were treated with rituximab, and 6 were treated with rapamycin initiated after diagnosis of APDS2. Five patients died from APDS2-related complications. Conclusion APDS2 is a combined immunodeficiency with a variable clinical phenotype. Complications are frequent, such as severe bacterial and viral infections, lymphoproliferation, and lymphoma similar to APDS1/PASLI-CD. Immunoglobulin replacement therapy, rapamycin, and, likely in the near future, selective phosphoinositide 3-kinase δ inhibitors are possible treatment options

Chronic low back pain syndrome

The aim of the study – to analyse the factors of chronic low back pain.Цель исследования - анализ факторов хронизации боли в нижней части спины