In Vivo and In Vitro Analysis of Toxicity of a Prospective Magnetic Resonance Contrast Agent Based on Arabinogalactan and Gadolinium Nanocomposite.

We studied the cytotoxic effect of gadolinium nanocomposite on cultured mouse fibroblasts 3T3-SV40 and histological changes in the liver tissue of albino rats after its administration. For in vitro experiment, gadolinium nanocomposite on the natural matrix of arabinogalactan (nGd-AG) was dissolved in DMEM nutrient medium to concentrations of 0.005, 0.02, 0.5, 2, and 5 mM. In in vivo experiment, a nGd-AG solution was orally administered to rats through a tube in a dose of 500 µg Gd/kg in 1 ml of 0.9% NaCl for 10 days. The pattern and degree of influence of the gadolinium nanocomposite on the studied cell culture depended on the concentration and duration of exposure. IC50 of nGd-AG determined after cell incubation for 24, 48, and 72 h were 616 µg/kg (3.9 mM), 302 µg/kg (1.9 mM), and 222 µg/kg (1.4 mM), respectively. Histological changes in the liver of white rats induced by exposure to nanocomposite attested to the development of a compensatory reaction of the organ.

Synthesis of 1-[ω-(Bromophenoxy)alkyl]-3-naphthalenylmethyl Derivatives of Uracil and Their Analogues As Probable Inhibitors of Human Cytomegalovirus Replication.

The synthesis of a new series of 1-[ω-(bromophenoxy)alkyl]-uracil derivatives containing in position 3 naphthalen-1-yl-, naphthalen-2-yl-, 1-bromonaphthalen-2-ylmethyl, benzyl, and anthracene 9-methyl fragment was carried out. The antiviral properties of the synthesized compounds were studied against human cytomegalovirus. It was found that the compound that contained a bridge of five methylene groups has a high anti-cytomegalovirus activity in vitro.

Reproductive Function of Male Rats and Motor Activity of Their Offspring in Fire Emissions Modeling.

We studied the reproductive function of albino male rats after long-term exposure to wildfire smoke and the species-specific behavior of their sexually mature offspring. After the end of exposure, the mean number of spermatogonia and the relative number of Leydig cells in rat testes decreased and the index of spermatogenesis decreased. The offspring of exposed males mated with intact females demonstrated impaired cognitive abilities and disturbances of species-specific behavior. The severity of these changes depended on time interval between the end of the inhalation exposure and mating.

Synthesis of 1-[ω-(Bromophenoxy)alkyl]-3-Naphthalenylmethyl Uracil Derivatives and Their Analogues as Probable Inhibitors of Human Cytomegalovirus Replication.

A new series of 1-[ω-(bromophenoxy)alkyl]-uracil derivatives containing naphthalen-1-yl, naphthalen-2-yl, 1-bromonaphthalen-2-ylmethyl, benzyl, and anthracene-9-ylmethyl fragments in position 3 of uracil residue was synthesized. The antiviral properties of the synthesized compounds against human cytomegalovirus were studied. It was found that the compound containing a bridge consisting of five methylene groups exhibits a high anti-cytomegalovirus activity in vitro.

Evaluation of the Antiviral Potential of Modified Heterocyclic Base and 5'-Norcarbocyclic Nucleoside Analogs Against SARS-CoV-2.

The pandemic caused by the novel betacoronavirus SARS-CoV-2 has already claimed more than 3.5 million lives. Despite the development and use of anti-COVID-19 vaccines, the disease remains a major public health challenge throughout the world. Large-scale screening of the drugs already approved for the treatment of other viral, bacterial, and parasitic infections, as well as autoimmune, oncological, and other diseases is currently underway as part of their repurposing for development of effective therapeutic agents against SARS-CoV-2. In this work, we present the results of a phenotypic screening of libraries of modified heterocyclic bases and 5'-norcarbocyclic nucleoside analogs previously synthesized by us. We identified two leading compounds with apparent potential to inhibit SARS-CoV-2 replication and EC50 values in a range of 20-70 µM. The structures of these compounds can be further optimized to develop an antiviral drug.

Synthesis and Antiviral Properties of 1-Substituted 3-[ω-(4-Oxoquinazolin-4(3H)-yl)alkyl]uracil Derivatives.

A series of uracil derivatives containing a 4-oxoquinazoline fragment bound to the nitrogen atom N3 of the pyrimidine ring by a short methylene bridge was synthesized to search for new antiviral agents. Some compounds in this series are shown to exhibit high inhibitory activity against human cytomegalovirus and the varicella zoster virus in a HEL cell culture.

[Informative value of ultrasound in the diagnosis of intraneural perineurioma]. / Informativnost' UZI v diagnostike intranevral'noi perinevriomy.

OBJECTIVE: To describe clinical and sonographic features of confirmed intraneural perineurioma in 5 patients. MATERIAL AND METHODS: We report clinical and sonographic features and retrospective follow-up data in 5 patients with intraneural perineurioma verified by biopsy. RESULTS: In all cases, symptoms were represented by a slowly progressive painless mononeuropathy with muscle atrophy and impaired tendon reflexes. Ultrasound examination revealed locally enlarged cross-sectional area of the nerve that was confirmed by intraoperative visualization. CONCLUSION: Intraneural perineurioma should be obligatory suspected in case of fusiform thickening of the nerve with locally changed echogenicity. Pooled multiple-center studies with large samples are needed to determine sensitivity and specificity of the main ultrasound parameters including changes in cross-sectional area and echogenicity of the nerve.

[Neurotization of the cornea as pathogenically targeted method of treating neurotrophic keratitis in patients with facial paralysis]. / Nevrotizatsiya rogovitsy kak patogeneticheski napravlennyi metod lecheniya neirotroficheskogo keratita u patsientov s litsevym paralichom.

Combined lesions of the facial and trigeminal cranial nerves are typical after neurosurgical treatment. Violation of the innervation of orbicularis muscle leads to inability to completely close the eyelids, while denervation of the cornea is often manifested as a long-term ongoing and recurring neurotrophic keratitis. The restoration of corneal innervation is a pathogenetically targeted treatment for this pathology. For this purpose, neurotrophic keratitis could be reversed via the method of corneal neurotization using contralateral n. ophthalmicus. The presented clinical case demonstrates the results of the first operation of neurotization of the cornea in a patient with combined lesions of the facial and trigeminal nerves.

[Mononeuropathy of dorsal interosseous nerve: compression by return radial arteries]. / Mononeiropatiia zadnego mezhkostnogo nerva: kompressiia vozvratnymi luchevymi arteriiami.

Among many causes of compression neuropathies involving the radial nerve, compression of the posterior interosseous nerve (PIN) by the returning radial arteries is rare. OBJECTIVE: To describe the clinical instrumental characteristics of cases of mononeuropathy caused by compression of the return radial arteries. MATERIAL AND METHODS: Two observations with neuropathy of the deep branch of the radial nerve, manifested by weakness in the corresponding muscles, inconsistent pain syndrome with previous stereotypic (recurring) physical activity are presented. RESULTS: According to the results of ultrasound examination of posterior interosseous nerve, a local hypoechogenic increase in the cross-sectional area of nerve of different lengths was revealed. During surgical decompression of the nerve, in the first case, a tight arterial loop was found around the nerve, in the second case, expanded arterial trunks, one of which, of small diameter, covered the nerve in the 'loop', and the other, larger, pierced the nerve. After the operation, regression of motor deficiency and relief of pain were noted.

[Sonographic characteristics of non-traumatic focal hourglass-like nerve constriction]. / Sonograficheskie kharakteristiki netravmaticheskoi fokal'noi konstriktsii nerva po tipu 'pesochnykh chasov'.

AIM: To describe the sonographic phenomenon of the focal 'hourglass-like constriction' of the peripheral nerves (FCPN). MATERIAL AND METHODS: The authors described 7 patients meeting the criteria for the diagnosis of neuralgic amyotrophy with unilateral FCPN identified with ultrasound in 4 cases and detected intraoperatively in 3 cases (preliminary ultrasound was not performed). The US scanner Sonoscape Pro mode gray scale in the transverse and longitudinal scanning, linear probe 8-15 MHz and Logiq9 scanner with elastography were used. RESULTS: FCPN was detected in the single nerve in 4 patients, in two nerves in 2 patients and in 3 nerves in one patient. Among all the nerves involved in the pathological process, the radial nerve and its branches were affected in 73% (8 nerves); the ulnar nerve was involved in 18% (2 nerves) and the musculo-cutaneous nerve in 9%. The length of the constriction of the peripheral nerve did not exceed 1.7 mm. The deformation coefficient (DC) of constriction area was 3.8 to .,9; the change in the elasticity in the form of an increase of DC to 5.9 when compared to the intact portion of the nerve and a decrease in echogenicity were observed in one patient. CONCLUSION: High-resolution ultrasound of the nerve can be an informative method for the diagnosis of idiopathic non-traumatic FCPN mononeuropathy.

1-(4-Phenoxybenzyl) 5-Aminouracil Derivatives and Their Analogues - Novel Inhibitors of Human Adenovirus Replication.

Adenovirus infections are characterized by widespread distribution. The lack of causal therapy, which is effective in treating this group of diseases, explains the need for new therapeutic drugs. Notably, anti-adenoviral activity of [4-(phenoxy)benzyl]-5-(phenylamino)-6-azauracil, 1-[4-(phenoxy)benzyl]-5-(morpholino) uracil, 1-[4-(4-chlorophenoxy)benzyl]-5-(morpholino) uracil, and 1-[4-(4-fluorophenoxy)-benzyl]-5-(morpholino) uracil was observed.

[Additive technologies in neurosurgery]. / Additivnye tekhnologii v neirokhirurgii.

Modern achievements of technical progress, in particular additive technologies (ATs) and three-dimensional printing, have been increasingly introduced in neurosurgical practice. The increasing complexity of surgical interventions requires thorough planning of surgery and a high level of training of young neurosurgeons. Creation of full-scale three-dimensional models for planning of surgery enables visualization of the anatomical region of interest. Additive technologies are especially extensively used in reconstructive surgery of skull defects. ATs enable fast and efficient solving of the following tasks: - generation of accurate models of the skull and an implant; - development and fabrication of individual molds for intraoperative formation of implants from polymeric two-component materials (e.g., PMMA); - fabrication of individual implants from titanium alloys or polyetheretherketone (PEEK) for further use in surgery.

Experimental lead intoxication symptoms with hyperglycemia state.

In lead intoxication model, with hyperglycenia state, atherogenicity coefficient reached 1,45 (1,35-1,85), if compared to 1,30 (0,85-1,40) in white rats exposed to lead. Heart rate reached 421,00 (411,00-468,00) per minute vs, 385,50 (359,00-399,50) per minute in animals died with lead intoxication, shorter median interval between QRS-complexes up to 143,00 (128,00-146,00) ms vs, 160,00 (150,50-169,00) ms was seen in animals exposed to lead.

Expression of caspase-3 and bcl-2 proteins as an indicator of functional state of brain tissue in white rats exposed to argentumarabinogalactane.

The article presents results on experimental modelling an influence of silver nanoparticles incorporated into natural polymer arabinogalactane matrix on brain tissue of white outbred rats. The rats underwent parenteral injection of silver nanoparticles incorporated into polymer arabinogalactane matrix (dosage of 100 and 500 micrograms of silver per kg of the animal weight). The studies covered expression of 2 proteins participating in apoptosis process, in mitochondrial activation type - caspase-3 and protein bcl-2. During experiment, the groups examined demonstrated significant dose-dependent effect of bcl- 2 protein expression and increased number of caspase-3 expressed and non-expressed hyperchromic cells under exposure to argentumarabinogalactane - that indicates disorders of cellular structure and apoptosis development.

[Induction of apoptosis in neurons of white rats under exposure of nanobiocomposite based on ag (0) nanoparticles and arabinogalactan].

There are presented results of the immunohistochemical study of neural tissue of outbred albino rats exposed for 9 days to the influence of the silver nanobiocomposite consisted of silver nanoparticles encapsulated into a matrix of a natural polymer - arabinogalactan. The research of albino rats was performed in 2 stages: half of the rats in each groups were decapitated immediately after the exposure (early period) and the rest animals - 6 months after the end of exposure (remote period). The impact of the studied substance was proved to cause functional changes in cells of the nervous tissue. After the subacute administration of the nanobiocomposite - argentum-arabinogalactan (nano-Ag-AG) in cells of the nervous tissue of the brain of albino rats the expression of apoptotic and anti-apoptotic protein (caspase-3 and bcl-2) was established to be changed. The number of normal neurons producing protein caspase-3 sharply increases. Herewith the number of immunonegative neurons fairly declines. Along with this there is noted the high level of bcl-2 content, one function ofwhich is the preclusion ofapoptosis. In preparations there is revealed a significant gain in the number of bcl-2 expressing neurons, however, the protective effect of the protein is not fully realized, that leads to the significantly increase in the content of damaged hyperchromatic cells. The evaluation of results of the immunohistochemical study of the nervous tissue of albino rats according to data concerning the proteins caspase-3 and bcl-2 expression permits to make a conclusion about the capability of nanoargentum encapsulated into polymer matrix by passing the blood-brain barrier to induce the triggering apoptosis cascade in neurons of the cerebral cortex.

5-Arylaminouracil Derivatives as Potential Dual-Action Agents.

Several 5-aminouracil derivatives that have previously been shown to inhibit Mycobacterium tuberculosis growth at concentrations of 5-40 µg/mL are demonstrated to act also as noncompetitive non-nucleoside inhibitors of HIV-1 reverse transcriptase without causing toxicity in vitro (MT-4 cells) and ex vivo (human tonsillar tissue).

[Evaluation of biologic effects caused by nano-silver influence on brain tissue of experimental animals].

The article presents results of histologic and immunohistochemical examination of nerve tissue of outbred white rats subjected over 9 days to nanobiocomposite containing nanoparticles of silver and natural biopolymer arabinogalactane. Exposure to the studied chemical was proved to cause structural and functional changes in nervous tissue. Comparing results of structural study of nervous tissue with expression of proteins caspase-3 and bcl-2 proves ability of nanosilver incapsulated into polymer matrix to penetrate through blood-brain barrier and induce apoptosis in neurons of brain cortex.

2-(2,4-Dioxy-1,2,3,4-Tetrahydropyrimidin-1-yl)-N-(4-Phenoxyphenyl)-Acetamides as a Novel Class of Cytomegalovirus Replication Inhibitors.

A series of novel uracil derivatives, bearing N-(4-phenoxyphenyl)acetamide moiety at N3 of a pyrimidine ring, has been synthesized. Their antiviral activity has been evaluated. It has been found that the novel compounds possess high inhibitory activity against replication of human cytomegalovirus (AD-169 and Davis strains) in HEL cell cultures. In addition, some of the derivatives proved to be inhibitory against varicella zoster virus.

[Alteration of white rats brain tissue inducted by assessment of silver nanocomposite incapsulated in polymer matrix].

The paper present experimental materials of intragastric administration of silver nanoparticles encapsulated in polymer matrix of arabinogalactan by white outbred male rats. Animals were injected "pure" arabinogalactan and colloid silver solution containing silver macroform separately for comparison. Research provided data about status of brain tissue at the impact of these substances on organism. Histological analysis revealed the presence of a pathological process, character and intensity of which varied depending on the type of injected material. Pathological process under the influence of silver-arabinogalactan characterized by appearance in brain tissue of perivascular edema and development of acute inflammation in formation of glial scars, swelling of vascular bundles in sum.