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1.
Vestn Otorinolaringol ; 89(1): 64-72, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38506028

RESUMO

Children's and adults' rhinosinusitis are two diseases that have both similarities and differences in anatomy, epidemiology, causes, pathogenesis, diagnosis and treatment. At the same rhinosinusitis is one of the most common in otorhinolaryngology's practice, both in children and adults. The of adults paranasal sinuses (PNS) anatomy differs from children's PNS anatomy. Although ostiomeatal complex occlusion is recognized as a major cause of poor ventilation and drainage of the adult paranasal sinuses, it does not have a strong effect on pediatric rhinosinusitis, but adenoids play a key role. Adenoids are bacteria and biofilms reservoirs that cause chronic refractory rhinosinusitis regardless of pharyngeal tonsil size. The prevalence of chronic rhinosinusitis (CRS) is lower in children than in adults. Diagnosis of children's rhinosinusitis is more difficult because nasal cavity endoscopic examination is performed rarely due to the occasional need of general anesthesia during the procedure. Moreover, it's necessary to take into account prevailing etiological role of viruses in ARS at children's age and chronic adenoiditis often accompanies pediatric CRS, which requires attention prescribing medical therapy as the basis of rhinosinusitis treatment. The DysheLORz based on Pelargonium sidoides roots is highly effective and safe for children's and adults ARS and CRS treatment, both as monotherapy and in combination with topical steroids and antibiotics. This herbal medicine immunomodulatory effect is mediated mainly by stimulating the production of TNF-α, IL-1, IL-12 and IFN-γ. It activates macrophages and improves their phagocytic activity. IL-12, together with TNF-α, enhances NK and cytotoxic CD8+ lymphocytes' activity against infected cells. IL-12 effect on Th1 lymphocytes maturation provides a link between innate and adaptive immunity. This is also increasing MCP-1, IP-10 and MIP-1ß chemokines synthesis and decreasing MIP-1α, ENA-78, GROα and IL-8 production in PNS and nasal mucosa. This leads to decrease of neutrophils chemotaxis to the inflammation site, and decline of serine proteases concentration (neutrophils main enzymes), that increases mucous membrane epithelial barrier permeability, reducing bacterial infections risk. Additionally, Pelargonium sidoides increases epithelial cells beating cilia frequency and inhibits hemagglutinin and neuraminidase present on influenza virus surface. The drug increases antimicrobial peptides production as defensins, human neutrophil peptides (HNP) and bactericidal permeability-increasing protein (BPI), which is also important for rapid inflammation regression in rhinosinusitis. It causes bacterial adhesion to epithelial cells inhibition, phagocytosis stimulation, nitric oxide (NO) release and oxidative burst. The medicine had a direct effect on Streptococcus pneumoniae, Staphylococcus aureus, Neisseria, Moraxella catarrhalis and Haemophilus influenza. Based on these data, it is possible to explain the high effectiveness and safety of the drugs based on Pelargonium sidoides in ENT organs inflammation treatment, for both adults and children over 1 year old.


Assuntos
Rinite , Rinossinusite , Sinusite , Adulto , Humanos , Criança , Lactente , Rinite/terapia , Rinite/tratamento farmacológico , Fator de Necrose Tumoral alfa , Sinusite/terapia , Sinusite/tratamento farmacológico , Mucosa Nasal , Inflamação , Interleucina-12/uso terapêutico , Doença Crônica
2.
Artigo em Inglês | MEDLINE | ID: mdl-35670387

RESUMO

The vaccination is a global issue of controlling infection agents and non-infectious diseases that require modern technologies and scientific knowledge. During the COVID-19 pandemic the work is continuously implemented to control the situation. The vaccination can affects controlling outbreaks all around the world. Besides, applying several types of vaccines in various countries to control second peak of the pandemic can be considered as significant factor that positively impacts host immune response. However, there are different barriers to vaccination programs worldwide in areas of economy, technology, politics, demography, psychology, especially in countries with low economic level. Although vaccination program started in many countries, developing mass immunity in society is essential for pandemic termination. Iran and Russia also are involved in COVID-19 pandemic disease since January 2020, and they are still working to achieve mass immunity. The actual study was carried out to compare vaccination extent between Russia and Iran countries to evaluate vaccination impact on the COVID-19 pandemic and to review some main factors that influence vaccination to understand main barriers of vaccination in both countries.


Assuntos
Vacinas contra COVID-19 , COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Humanos , Programas de Imunização , Irã (Geográfico)/epidemiologia , Pandemias/prevenção & controle , Federação Russa/epidemiologia , Vacinação
3.
Her Russ Acad Sci ; 91(5): 516-524, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744395

RESUMO

Features of demographic development in Russia from the 1940s to 2020 are retrospectively considered. The stages of the country's demographic development are analyzed, including the contribution of various components to the demographic dynamics in certain historical periods. The idea of distinguishing two waves of depopulation is proposed, and it is argued that the second wave of depopulation in Russia is provoked not only by negative modern trends, but is also associated with the historical features of the demographic development of the country, namely, with the age structure of the population, deformed under the influence of various historical events, or with "demographic pitfalls," often referred to in the literature. The contribution of supermortality to depopulation in the 1990s, called the shock stage of Russia's demographic development, is highlighted. The features of the second wave of depopulation are noted, which are associated with a decrease in the number of women of reproductive age and a new round of increase in mortality due to COVID-19. A systematic approach to neutralizing the second wave of depopulation is substantiated on the basis of a comprehensive national demographic program, including a system of measures to create conditions for the birth and upbringing of children, support families with children, develop self-preserving behavior, reduce mortality, increase life expectancy, reduce emigration, and attract migrants of the necessary categories to Russia.

4.
Artigo em Russo | MEDLINE | ID: mdl-34665535

RESUMO

The pandemic of the new corona-virus infection COVID-19 will be over only when population immunity will be developed. This condition can be achieved by both vaccination and surviving disease in natural way. The WHO recommends the first mode for achieving population immunity, since immune response to vaccine is similar to that one developed while surviving natural infection, but with minimal risks to health and life. The article presents the results of sociological survey organized with purpose of studying the attitude of Russians to vaccination against COVID-19 infection. The results of the survey demonstrated that at present, 22% of respondents are ready to be vaccinated i.e. they responded positively to the corresponding question. The following main factors determining population attitude to vaccination were identified. First, there is statistically significant correlation between vaccination readiness and education level: respondents with higher level of education are more likely to be vaccinated against COVID-19. Secondly, in general, the population is quite positive about the response of the National health care to the corona-virus pandemic. However, the percentage of population that is positive about vaccination can be higher if it would be possible to apply foreign-made vaccines in Russia. Thirdly, still there is large percentage of population believing that vaccination with medications that have not passed long-term clinical trials can result in health negative consequences. Fourthly, the majority of respondents experienced various manifestations of the pandemic on themselves: either they have been ill themselves, or their relatives and friends were ill or died and almost all of them somehow limited their common mobility.The survey results did not established statistically significant differences in distribution of responses among males and females. We assume that in order to develop positive attitude of population to vaccination, and specifically to Russian-made vaccines, more extensive information campaign is needed to be implemented. Also, significant increase of percentage of vaccinated population can be achieved if clearly defined requirements for availability of COVID-19 vaccination would be adopted on the international level. Actually, this is key condition for restoring international mobility and removing restrictions in national economies.


Assuntos
COVID-19 , Vacinas contra COVID-19 , Demografia , Feminino , Humanos , Masculino , Pandemias , Federação Russa/epidemiologia , SARS-CoV-2 , Vacinação
5.
Vestn Otorinolaringol ; 86(4): 17-22, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34499442

RESUMO

THE PURPOSE OF THE STUDY: To determine the value of the results of various audiological and vestibulometric studies for the differential diagnosis of non-inflammatory perilymphatic fistulas of the labyrinth windows (PFOLW). MATERIAL AND METHODS: The retrospective and prospective analysis of the informative value of the results of audiological and vestibulometric studies was carried out in 124 people with different combinations of cochleovestibular complaints, who had different pathology of the inner and middle ear, with different terms of the disease - from several days to 30 years. To assess the informativeness of the applied testing, the following operational characteristics were determined: general sensitivity (Se), specificity (Sp) and the prognostic value of a positive result (PPV=positive predictive value). A pair-by-pair comparison of the prognostic value of a positive result of vestibulometric and audiometric tests was performed using the Pearson criterion χ2 and the exact Fisher criterion. RESULTS: It is shown that none of the tests used has 100% reliability, but the consistent application of some of them can successfully improve the diagnosis of idiopathic PFOL. When comparing the results of a number of tests, such as the Fukuda walking test and / or the Babinsky-Weil walking test, audiometric tests with head clone and hyperventilation, the test of fluid injection into the external auditory canal and the test of J. Frasser & L. Flood, it was found that the average prognostic value of a positive result was 87.3%, which is statistically significantly higher than the average result (47.9%) for other samples. CONCLUSIONS: Correlations of the results of simple vestibulometric and audiometric tests allow us to recommend them to improve the diagnosis of idiopathic perilymphatic fistulas of the labyrinth windows. The possibilities of modern electrophysiological audiological research methods are subject to further study.


Assuntos
Fístula , Doenças do Labirinto , Diagnóstico Diferencial , Fístula/diagnóstico , Humanos , Doenças do Labirinto/diagnóstico , Perilinfa , Reprodutibilidade dos Testes , Estudos Retrospectivos
6.
Artigo em Russo | MEDLINE | ID: mdl-34190464

RESUMO

The article considers the historical features of development and theoretical approaches to defining the concept of "pandemic" in social sciences. The approaches of demographic science to the study of the consequences of pandemics are outlined. The prerequisites of occurrence of major pandemics at various historical stages of humankind development are highlighted. The particular attention is paid to pandemics in the XXI century. The demographic and social economic consequences of pandemics for the countries all over the world, including the countries on post-Soviet territory, are considered. The characteristics of the COVID-19 pandemic are highlighted from the standpoint of social demographic consequences, including the impact on fertility and mortality. The key directions of pandemics control in some countries of the world are designated.


Assuntos
COVID-19 , Pandemias , Demografia , Fertilidade , Humanos , SARS-CoV-2
7.
Nat Commun ; 12(1): 762, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536408

RESUMO

The shaping of astrophysical outflows into bright, dense, and collimated jets due to magnetic pressure is here investigated using laboratory experiments. Here we look at the impact on jet collimation of a misalignment between the outflow, as it stems from the source, and the magnetic field. For small misalignments, a magnetic nozzle forms and redirects the outflow in a collimated jet. For growing misalignments, this nozzle becomes increasingly asymmetric, disrupting jet formation. Our results thus suggest outflow/magnetic field misalignment to be a plausible key process regulating jet collimation in a variety of objects from our Sun's outflows to extragalatic jets. Furthermore, they provide a possible interpretation for the observed structuring of astrophysical jets. Jet modulation could be interpreted as the signature of changes over time in the outflow/ambient field angle, and the change in the direction of the jet could be the signature of changes in the direction of the ambient field.

8.
Artigo em Russo | MEDLINE | ID: mdl-33338331

RESUMO

As coronavirus quarantine period is increasing, concerns are growing about its possible impact on international migrants and students. The article discusses the basics of quarantine concept and its impact during COVID-19 pandemic. The purpose of study is to develop scale to determine relationship between such factors as financial stability, living condition, educational condition, social life and physiological reactions with psychological stability and life satisfaction of international students in Russia. The focus is done on international students of Russian universities. The questionnaires (n=300) were distributed among target respondents using the convenience random sampling technique. The analysis of survey results established relationship between the factors mentioned above and international students' psychological stability and life satisfaction. The study results proved that the original scale applied in this study is reliable and valid to assess level of life satisfaction. Therefore, policy makers should resolve related problems, including financial incentives, availability of such products as food and hygiene products through applying proper and sufficient information about the situation. using distance learning technologies, communication tools to insure positive impact on life satisfaction of international students. Moreover, the study results can provide to prospect researchers in the field of life satisfaction and psychological stability reliable and useful information.


Assuntos
COVID-19 , Coronavirus , Humanos , Pandemias , Satisfação Pessoal , Quarentena , Federação Russa , SARS-CoV-2 , Estudantes , Inquéritos e Questionários
9.
Vestn Otorinolaringol ; 85(2): 26-30, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32476385

RESUMO

THE OBJECTIVE: Of the work was to describe the basics of a meta-analysis with features for evaluating models with fixed and random effects, to present principles for interpreting the graphical results of a meta-analysis (forest plot or blobogram) of comparative reviews of randomized clinical trials (RCTs). MATERIAL AND METHODS: To illustrate the possibility of efficient use of the R software environment for meta-analysis, we used the results of RCTs of various tonsillectomy methods already published in the Cochrane Database review. RESULTS: The article provides explanations for the calculation of effect size, heterogeneity statistic, and other meta-analysis statistics and their interpretation for evaluating RCTs and recommendations for choosing a model depending on the on the general research concept. CONCLUSION: The described method allows meta-analysis and gives an idea of the principles for preparing the results of clinical trials with the expectation of their subsequent use in systematic reviews and meta-analysis.


Assuntos
Otolaringologia
10.
Phys Rev E ; 101(4-1): 043208, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32422777

RESUMO

The formation of high energy density matter occurs in inertial confinement fusion, astrophysical, and geophysical systems. In this context, it is important to couple as much energy as possible into a target while maintaining high density. A recent experimental campaign, using buried layer (or "sandwich" type) targets and the ultrahigh laser contrast Vulcan petawatt laser facility, resulted in 500 Mbar pressures in solid density plasmas (which corresponds to about 4.6×10^{7}J/cm^{3} energy density). The densities and temperatures of the generated plasma were measured based on the analysis of x-ray spectral line profiles and relative intensities.

11.
Vestn Otorinolaringol ; 84(2): 36-39, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31198213

RESUMO

The purpose of this study was to investigate the effectiveness of the use of natural preparations Tonsilotren and Cinnabsin (T & C therapy) in the complex treatment of chronic adenoiditis in children. In the control group, children received standard anti-inflammatory therapy. The high efficacy of the combined intake of Tonzilotren and Cinnabsin drugs (T & C therapy), the use of which led not only to the disappearance of signs of chronic adenoiditis, but also to a significant decrease in the size of the pharyngeal tonsil, which allowed to avoid surgical treatment.


Assuntos
Tonsila Faríngea , Tratamento Conservador , Nasofaringite , Criança , Doença Crônica , Humanos , Nasofaringite/terapia
12.
Vestn Otorinolaringol ; 83(3): 56-60, 2018.
Artigo em Russo | MEDLINE | ID: mdl-29953057

RESUMO

The main objectives of the present article were to systematize the modern views of the causes and risk factors of allergic rhinitis, to clarify the manner of its development, to define the leading etiological mechanism underling the pathogenesis of this condition, to consider the methods used for the diagnostics and the treatment of this disease, and to sum up the clinical experience with the use of Levocetirizine (Allerwey) for the management of allergic rhinitis. Special attention is given to the achievement and the maintenance of control of the persistent or intermittent forms of allergic rhinitis and to approaches to its treatment based on the medications registered in the Russian Federation.


Assuntos
Cetirizina , Obstrução Nasal , Rinite Alérgica , Cetirizina/administração & dosagem , Cetirizina/efeitos adversos , Antagonistas não Sedativos dos Receptores H1 da Histamina/administração & dosagem , Antagonistas não Sedativos dos Receptores H1 da Histamina/efeitos adversos , Humanos , Testes Imunológicos/métodos , Obstrução Nasal/fisiopatologia , Obstrução Nasal/terapia , Administração dos Cuidados ao Paciente/métodos , Rinite Alérgica/classificação , Rinite Alérgica/epidemiologia , Rinite Alérgica/imunologia , Rinite Alérgica/terapia , Resultado do Tratamento
13.
Adv Gerontol ; 31(6): 988-995, 2018.
Artigo em Russo | MEDLINE | ID: mdl-30877833

RESUMO

The article analyzes structure of forensic medical research of persons older than working age and its change during period of improving social and economic situation in the country. Persons whose causes of death are determined by forensic medical examination are considered as a deviant group of people who did not adapt to changing socio-cultural conditions and to age changes. That was manifested in causes and circumstances of death (external causes, death at home without witnesses, death on street or in hospital without examination). The information on 72 324 forensic examinations of elderly residents in Nizhny Novgorod region for 2003-2017 was analyzed. It was done in terms of sex, living or not in the regional center and age groups (advanced: 60-74 years for men and 55-74 years for women, senile: 75-84 years, age of longevity: 85 years and older). It is shown that the size of the deviant group of retirees is increasing, and this increase is not a consequence only of the population aging. The contribution of loneliness to formation of the deviant group exceeds the contribution of socioeconomic disadvantages: no correlation was found between the frequency of forensic examinations and the mortality from causes related to alcohol; from 2003 to 2017, the share of external death causes and the proportion of corpses taken for examination from street are decreasing. The structure of external and somatic death causes of persons older than working age established during forensic medical research is determined by age, place of residence as well as social and economic situations in the region, changing for the period studied in direction of reducing differences.


Assuntos
Causas de Morte , Patologia Legal , Carência Psicossocial , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Federação Russa
14.
Phys Rev Lett ; 119(25): 255002, 2017 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-29303310

RESUMO

We investigate the formation of a laser-produced magnetized jet under conditions of a varying mass ejection rate and a varying divergence of the ejected plasma flow. This is done by irradiating a solid target placed in a 20 T magnetic field with, first, a collinear precursor laser pulse (10^{12} W/cm^{2}) and, then, a main pulse (10^{13} W/cm^{2}) arriving 9-19 ns later. Varying the time delay between the two pulses is found to control the divergence of the expanding plasma, which is shown to increase the strength of and heating in the conical shock that is responsible for jet collimation. These results show that plasma collimation due to shocks against a strong magnetic field can lead to stable, astrophysically relevant jets that are sustained over time scales 100 times the laser pulse duration (i.e., >70 ns), even in the case of strong variability at the source.

15.
Radiats Biol Radioecol ; 56(1): 73-80, 2016.
Artigo em Russo | MEDLINE | ID: mdl-27245007

RESUMO

The influence of UV-light (240-390 nm) at dozes of 151 and 755 J/m2 on the content of membrane markers of lymphocytes using the method of flow cytometry was investigated. It was demonstrated that during incubation of UV-irradiated lymphocytes the change of their populational and sub-populational composition occurs. Expression of complexes of CD3, CD 19,.CD8, CD 16, CD25 and CD95 increased. This increase was caused mainly by de novo synthesis. UV-light had immunostimulating effect on CD8+ T-lymphocyte population. Together with the increase of cytotoxic cells and NK-cells, activation of lymphocytes (increased amount of CD25+ and CD95+ cells) took place. Amount of cells undergone apoptosis or necrosis increased proportionally to the dosage. These changes were more expressed during incubation of lymphocytes in nutrition medium without autological blood serum, e.g. under deficiency of growth factors and antioxidants.


Assuntos
Antígenos CD/efeitos da radiação , Apoptose/efeitos da radiação , Biomarcadores/sangue , Linfócitos/efeitos da radiação , Antígenos CD/sangue , Doadores de Sangue , Citometria de Fluxo , Humanos , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/efeitos da radiação , Linfócitos/metabolismo , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/efeitos da radiação , Raios Ultravioleta
16.
Vestn Otorinolaringol ; 80(4): 81-84, 2015.
Artigo em Russo | MEDLINE | ID: mdl-26525330

RESUMO

The results of clinical studies giving evidence of the therapeutic effectiveness of the mucoactive preparations for the treatment of rhinosinusitis made it possible to introduce the herbal medicinal product Myrtol into the European position paper on rhinosinusitis and nasal polyps (EPOS 2012). It was shown that the intake of Myrtol standardized preparation accelerates the regress of clinical symptoms of the disease, decreases the requirement for antibiotic therapy, and reduces the period of disability as compared with the similar effects of placebo.

17.
Radiats Biol Radioecol ; 55(6): 616-24, 2015.
Artigo em Russo | MEDLINE | ID: mdl-26964347

RESUMO

The flow-cytometric analysis of condition of human peripheral blood lymphocytes in dynamics of development of the apoptosis induced by exposure to UV-light (240-390 nanometers) at a dose of 1510 J/m2 was carried out. Superficial architectonics and changes of the level of a membrane potential and functional activity of succinatedehydrogenase of mitochondrions are studied. The contribution of extracellular calcium to the processes of lymphocyte cellular death is revealed. The ideas about dynamics of the intracellular events leading to the death of photomodified lymphocytes 1-6 h after their UV-radiation exposure are specified and added on the basis of the analysis of our new and already published results.


Assuntos
Apoptose/efeitos da radiação , Fragmentação do DNA/efeitos da radiação , Linfócitos/efeitos da radiação , Raios Ultravioleta , Cálcio/metabolismo , Técnicas de Cultura de Células , Células Cultivadas , Meios de Cultura/química , Relação Dose-Resposta a Droga , Citometria de Fluxo , Humanos , Linfócitos/metabolismo , Linfócitos/patologia , Linfócitos/ultraestrutura , Mitocôndrias/enzimologia , Mitocôndrias/efeitos da radiação , Mitocôndrias/ultraestrutura , Succinato Desidrogenase/metabolismo , Fatores de Tempo
18.
J Neurosci ; 21(23): 9291-303, 2001 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-11717363

RESUMO

Although intradendritic protein synthesis has been documented in adult neurons, the question of whether axons actively synthesize proteins remains controversial. Adult sensory neurons that are conditioned by axonal crush can rapidly extend processes in vitro by regulating the translation of existing mRNAs (Twiss et al., 2000). These regenerating processes contain axonal but not dendritic proteins. Here we show that these axonal processes of adult sensory neurons cultured after conditioning injury contain ribosomal proteins, translational initiation factors, and rRNA. Pure preparations of regenerating axons separated from the DRG cell bodies can actively synthesize proteins in vitro and contain ribosome-bound beta-actin and neurofilament mRNAs. Blocking protein synthesis in these regenerating sensory axons causes a rapid retraction of their growth cones when communication with the cell body is blocked by axotomy or colchicine treatment. These findings indicate that axons of adult mammalian neurons can synthesize proteins and suggest that, under some circumstances, intra-axonal translation contributes to structural integrity of the growth cone in regenerating axons. By immunofluorescence, translation factors, ribosomal proteins, and rRNA were also detected in motor axons of ventral spinal roots analyzed after 7 d in vivo after a peripheral axonal crush injury. Thus, adult motor neurons are also likely capable of intra-axonal protein synthesis in vivo after axonal injury.


Assuntos
Axônios/metabolismo , Regeneração Nervosa/fisiologia , Neurônios Aferentes/metabolismo , Proteínas Ribossômicas/biossíntese , Actinas/metabolismo , Animais , Axônios/efeitos dos fármacos , Axônios/ultraestrutura , Células Cultivadas , Colchicina/farmacologia , Gânglios Espinais/citologia , Gânglios Espinais/metabolismo , Cones de Crescimento/efeitos dos fármacos , Cones de Crescimento/fisiologia , Microscopia Eletrônica , Microscopia de Vídeo , Compressão Nervosa , Regeneração Nervosa/efeitos dos fármacos , Proteínas de Neurofilamentos/genética , Proteínas de Neurofilamentos/metabolismo , Neurônios Aferentes/citologia , Neurônios Aferentes/efeitos dos fármacos , Fatores de Iniciação de Peptídeos/metabolismo , Biossíntese de Proteínas/fisiologia , Inibidores da Síntese de Proteínas/farmacologia , RNA Mensageiro/metabolismo , RNA Ribossômico/metabolismo , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/fisiologia
19.
Nat Cell Biol ; 2(12): 958-63, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11146663

RESUMO

Clathrin-coated vesicles mediate diverse processes such as nutrient uptake, downregulation of hormone receptors, formation of synaptic vesicles, virus entry, and transport of biosynthetic proteins to lysosomes. Cycles of coat assembly and disassembly are integral features of clathrin-mediated vesicular transport (Fig. 1a). Coat assembly involves recruitment of clathrin triskelia, adaptor complexes and other factors that influence coat assembly, cargo sequestration, membrane invagination and scission (Fig. 1a). Coat disassembly is thought to be essential for fusion of vesicles with target membranes and for recycling components of clathrin coats to the cytoplasm for further rounds of vesicle formation. In vitro, cytosolic heat-shock protein 70 (Hsp70) and the J-domain co-chaperone auxilin catalyse coat disassembly. However, a specific function of these factors in uncoating in vivo has not been demonstrated, leaving the physiological mechanism and significance of uncoating unclear. Here we report the identification and characterization of a Saccharomyces cerevisiae J-domain protein, Aux1. Inactivation of Aux1 results in accumulation of clathrin-coated vesicles, impaired cargo delivery, and an increased ratio of vesicle-associated to cytoplasmic clathrin. Our results demonstrate an in vivo uncoating function of a J domain co-chaperone and establish the physiological significance of uncoating in transport mediated by clathrin-coated vesicles.


Assuntos
Vesículas Revestidas por Clatrina/metabolismo , Clatrina/metabolismo , DNA Fúngico/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Fosfoproteínas/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas Adaptadoras de Transporte Vesicular , Sequência de Aminoácidos , Animais , Transporte Biológico Ativo , Proteínas Fúngicas/genética , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Modelos Biológicos , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/genética , Fosfoproteínas/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Saccharomyces cerevisiae/genética , Homologia de Sequência de Aminoácidos
20.
Mol Genet Metab ; 71(4): 573-80, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11136549

RESUMO

The Sanfilippo syndrome type B (MPS III B) is an autosomal recessive disease caused by deficiency of alpha-N-acetylglucosaminidase (EC 3. 2.1.50), one of the lysosomal enzymes required for the degradation of heparan sulfate. The disease is characterized by profound neurodegeneration but relatively mild somatic manifestations, and is usually fatal in the second decade. A mouse model had been generated by disruption of the Naglu gene in order to facilitate the study of pathogenesis and the development of therapy for this currently untreatable disease. Recombinant human alpha-N-acetylglucosaminidase (rhNAGLU) was prepared from secretions of Lec1 mutant Chinese hamster ovary cells. The enzyme, which has only unphosphorylated high-mannose carbohydrate chains, was endocytosed by mouse peritoneal macrophages via mannose receptors, with half-maximal uptake at ca. 10(-7) M. When administered intravenously to 3 month-old mice, rhNAGLU was taken up avidly by liver and spleen but marginally if at all by thymus, lung, kidney, heart, and brain (in order of diminishing uptake). The half-life of the enzyme was 2.5 days in liver and spleen. Immunohistochemistry and electron microscopy showed that only macrophages were involved in enzyme uptake and correction in these two organs, yet the storage of glycosaminoglycan was reduced to almost normal levels. The results show that the macrophage-targeted rhNAGLU can substantially reduce the body burden of glycosaminoglycan storage in the mouse model of Sanfilippo syndrome III B.


Assuntos
Acetilglucosaminidase/uso terapêutico , Modelos Animais de Doenças , Mucopolissacaridose III/enzimologia , Mucopolissacaridose III/terapia , Acetilglucosaminidase/deficiência , Acetilglucosaminidase/genética , Acetilglucosaminidase/farmacologia , Animais , Endocitose , Deleção de Genes , Glicosaminoglicanos/metabolismo , Meia-Vida , Heparitina Sulfato/metabolismo , Humanos , Imuno-Histoquímica , Injeções Intravenosas , Fígado/citologia , Fígado/enzimologia , Fígado/metabolismo , Fígado/ultraestrutura , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/enzimologia , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Knockout , Microscopia Eletrônica , Mucopolissacaridose III/classificação , Mucopolissacaridose III/genética , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Baço/citologia , Baço/enzimologia , Baço/metabolismo
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