Ototoxic Effect of Nicotinamide Riboside.

We studied the function of the auditory system in Wistar rats after repeated intravenous administration of nicotinamide riboside (NR). The functional activity of the receptor and retrocochlear parts of the auditory system were assessed by recording short-latency auditory evoked potentials (SLAEPs) and distortion-product otoacoustic emissions (DPOAEs) at baseline, immediately after NR administration, and 1 and 2 months later. Repeated intravenous NR administration (cumulative dose of 2700 mg/kg) to Wistar rats has a detrimental impact on the structures within the cochlear section of the auditory system.

The Pattern of Granuloma Formation in the Liver of Rats as a Reflection of the Mechanism of Internalization of Submicron Silicon Particles.

A morphological analysis of the liver of Wistar rats was performed 2 months after a single intravenous injection of porous silicon particles of different sizes (60-80, 250-300, and 500-600 nm; 2 mg/ml, 1 ml). Histological, immunohistochemical, and electron microscopic methods showed the development of CD68+ granulomas in all experimental groups. Injection of 60-80-nm porous silicon particles led to the formation of single large granulomas (>2000 µm2), while 500-600-nm nanoparticles caused the formation of numerous smaller granulomas. The mechanism of involution of granulomas by apoptosis of Kupffer cells and the absence of subsequent connective tissue remodeling of the organ tissue is shown.

[«Our whole family does not get out of the common cold¼: an ear, throat and nose disease in the conditions of S.P. Botkin]. / «Vse nashe semeistvo ne vykhodit iz nasmorka¼: zabolevaniya ukha, gorla i nosa v okruzhenii S.P. Botkina.

The article presents an epistolary insight into the history of otorhinolaringology in Russia. It shows pathology of ear, nose and throat, which S.P. Botkin faced: cases of diseases of empress Maria Aleksandrovna, grand duke Vyacheslav Konstantinovich, poet N.A. Nekrasov, publisher A.A. Kraevsky, Sergey Petrovich himself, his relatives and loved ones. The biographical singularity of the famous doctor's patients is noted. On the materials of family letters of 1855-1889 yrs., service diaries of 1872-1889 yrs. and S.P. Botkin's clinical lectures it is shown how daily cases and casuistry of otorhinolaryngology pathology formed scientific innovative ideas.

[The most privy of all privy councilors in the Russian Empire: To the biography of Vyacheslav Avksentievich Manassein (1841-1901)].

The article, on the basis of archival documents introduced into scientific circulation, considers personality of prominent Russian physician Vyacheslav Avksentievich Manassein (1841-1901), who held the position of professor of the therapeutic Chairs of the Medical Surgical Academy in 1875-1892. The Manassein's public activity had special character, reaching All-Russian scale owing to the weekly "The Physician" published by him in 1880-1901. The article considers various aspects related to the scientific school of S. P. Botkin. For the first time, it is reported about the facts shedding light on complicated relationship of S. P. Botkin with his student V. A. Manassein.

"The letters of S. P. Botkin from Bulgaria. 1887": The return of the manuscript in Russia.

The previous report partially brought to light history of publishing of "The letters of S. P. Botkin from Bulgaria 1877". The original letters were abroad for many years and they were returned to the USSR in 1974 by grandchildren of S. P. Botkin, S. P. Chekhov and D. P. Chekhov, who resided in France. The circumstances of handing over of the letters to the N. A. Semashko Institute of Health Organization and Social Hygiene are presented. The letters have not been republished for 130 years, but their historical, moral and educational significance remains actual and nowadays. The modern edition of the complete manuscript, along with introductory article and detailed scientific commentary, will become a significant contribution to representation of biography of S.P Botkin, to supplementation of written sources about the Russian-Turkish war of 1877-1878, and to comprehension of centuries-old Middle Eastern geopolitics of Russia.

["The letters of S. P. Botkin from Bulgaria. 1877": The history of publication of autograph].

The letters of S. P. Botkin from Bulgaria (1877) to his wife, E. A. Botkina (née Princess Obolenskaya), were published as travel diary in the journal "Vestnik Evropy" in 1892 and as separate book in 1893. The family events related to publication of epistolary were restored. For publication, material of private nature was abridged by E. A. Botkina. Then, passages with compromising criticism were removed by editor of the journal. In spite of good quality of prepared text, publication was postponed by E. A. Botkina herself and afterwards it was lingered on because of claims of censorial department. The role of N. A. Belogolovy, public figure and friend of S. P. Botkin of many years and M. M. Stasyulevich, a publisher, in final decision to publish epistolary is emphasized. The comparison of original and printed matter carried out for the first time, established that cuts made up to more than one third of author's text.

Morphological Analysis of the Respiratory Tract of Rats after Parenteral Administration of Silicon Dioxide Nanoparticles.

Morphological analysis of the respiratory tract of Wistar rats was performed after a single parenteral administration of 12-nm silicon dioxide nanoparticles (1 ml, 2 mg/ml, intravenously) was performed. On day 21 and in 2, 4, and 6 months after the administration of nanoparticles, the development of macrophage infiltration in the interstitium of the respiratory tract was demonstrated by histological and immunohistochemical methods. The pool of alveolar macrophages increased in 4 months after administration (p=0.004) and returned to the control values in 6 months. The number of mast cells did not significantly change at all stages of the experiment. Connective tissue remodeling in the interstitium of the respiratory tract was not observed throughout the observation period.

Reaction of the Palatine Tonsillar Immunocompetent Cells to Irrigation of Crypts by Suspension of Silica Nanoparticles under Conditions of Chronic Tonsillitis.

We studied the response of neutrophils, macrophages, and mast cells to local application of silica nanoparticles (10-20 nm). Histological examination of tonsillar postoperative material from 6 patients aged 24-44 years with recurrent tonsillitis was carried out. Irrigation of the tonsillar lacunae was carried out over 5 days before bilateral tonsillectomy: on the right by Polysorb MP suspension (1 g/liter), on the left by saline. The contact of nanoparticles with the mucosa led to a decrease in the number of cells expressing myeloperoxidase (p=0.02) and an increase in the count of CD68+ cells (p=0.04); the count of mast cells remained unchanged. Local use of medical adsorbent based on silica nanoparticles induced changes in cells due to their resorption by the tissue. Positive chemotaxis of CD68+ macrophages revealed in the tonsillar lymphoid tissue attested to stimulation of non-specific immunity and inductive phase of specific immunity. The authors hypothesized that internalization of medical nanoparticles by resident phagocytes of the mucosa could support targeted biodistribution of drugs in the palatine tonsils.

Potentiation of Otoprotective Effect of Hydrocortisone Immobilized on Povidone Nanoparticles under Conditions of Intravenous Injection.

The otoprotective effect of immobilized hydrocortisone was studied on the model of acute acoustic injury to the auditory analyzer in male Wistar rats. The effects of true solution and suspension where polyvinylpyrrolidone particles (100-500 nm) served as dispersed phase (hydrocortisone concentration 5 mg/kg). The agents were administered immediately after continuous acoustic stimulation: 5 kHz tone, 110 dB for 2 h. The hearing status was evaluated by the amplitude of otoacoustic emission at the distortion product frequency (4-6.4 kHz) 1 and 24 h and 7 days after acoustic stimulation. Single injection of hydrocortisone suspension caused a more pronounced therapeutic effect within 1 day after acoustic stimulation.

[Last years of N. I. Pirogov (according to dairy of D. A. Skalon written in 1876-7878)].

Last years of N.I.Pirogov (according to dairy of D.A.Skalon written in 1876-1878). Excerpts from colonel D.A. Skalon's 1876-1878 diaries are published for the first time. The diaries detail his interactions with NI. Pirogov (1810-1881) and present a unique account on psychophysical state of the great Russian surgeon during the last years of his life. The testimony of an immediate witness pictures a hale old man with a choleric temperament, broad and creative mind, state-scale thinking, and diverse interests reaching far beyond medicine.

[Pre- and post-conditioning phenomena: the protective physiological mechanisms in the aspect of pathogenesis and the theory of treatment of ENT pathology].

The objective of the present work was to expose the universal general biological significance of the protective pre- and postconditioning phenomena and to provide an insight into the possibility of application of therapeutic modalities based on these effects in current otorhinolaryngological practice. Pre- and postconditioning phenomena (Pre-C and Post-C respectively) began to be studied as protective physiological mechanisms since the 1980s, first in cardiology and thereafter in other fields of experimental medicine. At the same time, their protective properties had been known and intuitively used much earlier among the established human cultural and social stereotypes, psychophysical training techniques, and methods of traditional and empirical medicine. The widespread application of these phenomena gives evidence of their universal biological nature as factors involved in the interactions between the organism and pathogens (including co-morbidity), the process leading to the enhancement of non-specific resistance, mechanisms underlying realization of pharmacodynamic effects of a number of pharmaceutical products,etc. The understanding of the protective potential of PreC and PostC dictates the necessity to revise and further elaborate the present-day strategy of prophylaxis and treatment of the most serious chronic ENT diseases.

[Ototoxicity of cisplatin].

The objective of this publication is to summarize "classical" and modern concepts of pathogenesis, clinical features of cisplatin ototoxicity, its screening, and prophylaxis. It is argued that pathogenesis of a cisplatin-induced injury to the inner ear shares common features with the ototoxic mechanisms of action of other pharmaceuticals even though it is characterized by certain important differences. The authors consider the mechanisms of ototropicity, specific cytochemical aspects of cisplatin cytotoxicity that aggravate risk factors, and genetic predisposition to the development of iatrogenic problems. The data are presented on monitoring and experimental aspects of otoprotection for the prevention of cisplatin-induced damage to the auditory analyzer.

[Analysis of mitochondrial 12S rRNA and tRNA(Ser(UCN)) genes in patients with nonsyndromic sensorineural hearing loss from various regions of Russia].

Mitochondrial DNA (mtDNA) mutations play an important role in etiology of hereditary hearing loss. In various regions of the world, patients suffer from nonsyndromic sensorineural hearing loss initiated by aminoglycoside antibiotics. Mutations that had been shown as pathogenetically important for hearing function disturbance were identified in mitochondrial 12S rRNA and tRNA(Ser(UCN)) genes while pathogenic role of several DNA sequences requires additional studies. This work presents the results of studying the spectrum of mutations and polymorphic variations in mtDNA genes 12S rRNA and tRNA(Ser(UGN)) in 410 patients with nonsyndromal sensoneural hearing impairment/loss from the Volga Ural region, St Petersburg, Yakutia, and Altai and in 520 individuals with normal hearing, which represent several ethnic groups (Russians, Tatars, Bashkirs, Yakuts, Altaians) residing in the Russian Federation. Pathogenetically significant mutation A1555G (12S rRNA) was found in two families (from Yakutia and St Peresburg) with hearing loss, probably caused by treatment with aminoglucosides, and in the population sample of Yakuts with a frequency of 0.83%. Further research is needed to confirm the role in hearing impairment of mutations 961insC, 961insC(n), 961delTinsC(n), T961G, T1095C (12S rRNA) and G7444A, A7445C (tRNA(Ser(UGN revealed in the patients. In addition, in the patients and the population groups, polymorphic mt DNA variants were detected, which are characteristic also of other Eurasian populations both in spectrum and frequency.

Pathomorphological peculiarities of damage to hair cells of the organ of corti in experimental sensorineural hearing loss.

Pathomorphology of the organ of Corti was studied on models of acute and chronic sensorineural damage to the acoustic analyzer. Peculiarities of hair cell degeneration, necrosis, and apoptosis in the organ were studied by light and scanning electron microscopy. The type of pathomorphological substrate in abnormalities of the organ of Corti depends on the intensity of the destructive exposure, but not on the nature of otopathological factors.

Protective effect of carnosine on excitable structures of the auditory apparatus in albino rats with acute acoustic trauma.

We studied the effect of natural antioxidant carnosine on Wistar rats with experimental acoustic trauma of the auditory apparatus. Repeated intraperitoneal injection of carnosine in a dose of 200 mg/kg 12 and 0.5 h before modeling of acute acoustic trauma decreased the severity of degenerative and atrophic changes in the nuclei of hair cells in the cochleae. Carnosine compensated the deficiency of tissue antioxidant systems and suppressed generation of lipid peroxidation products in tissues of the membranous cochlea and auditory cortex of the temporal lobes. Carnosine holds much promise as a nonspecific otoprotector.

[General pathological aspects of the hair cells damage in spiral organ]. / Obshchepatologicheskie aspekty povrezhdeniia voloskovykh kletok spiral'nogo organa.

The information concerning general pathological changes in hair cells of the spiral organ is reviewed. The conditions for the onset, morphological picture of dystrophy, necrosis, apoptosis typical for hair cells in respect to structural and functional features of the sensory epithelium of the spiral organ are outlined. Nonspecific morphological changes of the spiral organ neuroepithelium after the action of damaging agents of different origin (such ototoxic drugs as aminoglycoside antibiotics and others, intensive acoustic impacts, ageing of the acoustic analyzer) are emphasized.

Natural antioxidant L-carnosine inhibits LPO intensification in structures of the auditory analyzer under conditions of chronic exposure to aminoglycoside antibiotics.

Intragastric administration of L-carnosine suspension to Wistar-Kyoto rats 3 days before and after 7-day course of intraperitoneal injections of ototoxic aminoglycoside antibiotic kanamycin compensated expenditures of tissue antioxidant systems and significantly eliminated kanamycin-induced intensification of MDA production in tissues of the membrane part of the cochlea and in the auditory cortex of the temporal lobe. L-NAME (competitive NO synthase inhibitor) also inhibited LPO, increased total antioxidant activity, and decreased ototoxicity of kanamycin, which confirms the contribution of NO into LPO intensification under conditions of aminoglycoside treatment. Inhibition of pathological intensification of LPO processes and increase in total antioxidant activity under conditions of induced acute aminoglycoside ototoxicity characterizes L-carnosine as a highly effective otoprotector.