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1.
Bull Exp Biol Med ; 174(5): 585-588, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37040035

RESUMO

The course of bronchial asthma can be accompanied by cognitive impairments. However, the relationship between cognitive dysfunction and asthma has not been fully revealed, nor has it been fully established what causes cognitive impairments in patients with asthma. There is an opinion that transient hypoxia and persistent systemic inflammation with insufficient control of bronchial asthma can be accompanied by neurotoxicity in relation to the hippocampus and indirectly lead to deterioration of cognitive functions. Comorbid conditions, such as obesity, allergic rhinitis, and depressive states can increase cognitive dysfunction in asthmatics. The review considers the pathophysiology of cognitive dysfunction in patients with bronchial asthma, as well as the impact of comorbid conditions on the cognitive status. This information will allow systematizing the available knowledge about the state of cognitive functions in asthma for timely detection and correction of their impairments and, ultimately, optimization of the management of these patients.


Assuntos
Asma , Disfunção Cognitiva , Humanos , Cognição
2.
Bull Exp Biol Med ; 175(6): 715-719, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37978146

RESUMO

The number of people suffering from allergies is increasing worldwide every year. With the prevalence of domestic animals, especially dogs, allergens associated with them can be found ubiquitously, thereby increasing the risk of anaphylaxis in sensitized individuals. Currently, there are 8 known dog allergens, but not all of them have been thoroughly studied. The commonly used skin prick tests often fall short and fail to provide a comprehensive assessment of a patient's condition, thus making allergy diagnosis challenging. Fortunately, the introduction of new allergy diagnostic methods has made it possible to accurately identify clinically significant allergens for patients. These findings can then be used to prescribe appropriate therapy or provide specific recommendations to the patients. This review focuses on the most important dog allergens and modern allergy diagnostic techniques that are gradually being incorporated into medical practice, thus expanding the capabilities of allergists.


Assuntos
Anafilaxia , Patologia Molecular , Humanos , Cães , Animais , Imunoglobulina E , Alérgenos , Testes Cutâneos , Anafilaxia/diagnóstico
3.
Bull Exp Biol Med ; 176(1): 26-29, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38091134

RESUMO

We performed a comparative study of the parameters of chemiluminescence of blood neutrophils in patients with different severity of chronic obstructive pulmonary disease in its different periods. The maximum values of induced and spontaneous chemiluminescence were recorded at moderate severity of the disease during exacerbation. Low levels of chemiluminescence indicators were found in severe chronic obstructive pulmonary disease in the stable phase. The values of the induction period of the chemiluminescent response in patients with moderate chronic obstructive pulmonary disease were higher than in the control group. Correlations between the values of induced chemiluminescence of neutrophils and the respiration function parameter FEV1 were established, which may indicate the influence of multidirectional changes in the functional activity of systemic neutrophils on the development and worsening of airway obstruction in chronic obstructive pulmonary disease patients.


Assuntos
Neutrófilos , Doença Pulmonar Obstrutiva Crônica , Humanos
4.
Ter Arkh ; 95(7): 568-573, 2023 Sep 29.
Artigo em Russo | MEDLINE | ID: mdl-38159007

RESUMO

BACKGROUND: Dupilumab, a fully human monoclonal antibody directed against the common α-subunit of interleukin (IL)-4 receptors and blocking signaling from both IL-4 and IL-13, may be recommended for the treatment of moderate to severe atopic dermatitis (AD) and bronchial asthma (BA). AIM: To perform a comparative assessment of the effectiveness of maintenance therapy with dupilumab in patients with severe BA as the main indication for genetically engineered biological drugs and in patients with severe asthma with concomitant severe AD as the indication for targeted therapy. MATERIALS AND METHODS: A 6-month retrospective comparative study was performed at the specialized reference center for allergology and immunology. The study included 115 adult patients of both sexes treated with dupilumab for uncontrolled severe asthma as the main indication for targeted therapy (BA group; n=65) or for a combination of severe uncontrolled asthma and severe AD (BAAD; n=50). Dupilumab was administered subcutaneously for 6 months. The first dose was 600 mg once and then 300 mg Q2W. Evaluation of the effectiveness of dupilumab therapy at 6 months of treatment in both groups included achieving asthma control (ACT, ACQ5), improving pulmonary function test, reducing the risk of exacerbations and the need for systemic glucocorticosteroids (SGCS), improving quality of life (AQLQ), change of biomarkers (FeNO, eosinophil count) and the course of comorbid diseases, including improvement in the AD (SCORAD, EASI) and rhinosinusitis polyposa (SNOT-22). RESULTS AND CONCLUSION: During dupilumab therapy, in a significant proportion of patients, regardless of the presence or absence of other T2-associated diseases (e.g., AD or rhinosinusitis polyposa), an improvement in asthma was demonstrated as early as in the first 6 months of treatment with dupilumab in all recommended domains for assessing the response to targeted therapy: improving asthma control and respiratory function, reducing the frequency of moderate and severe exacerbations associated with the use of SGCS and/or hospitalization, a positive effect on the quality of life and the comorbid diseases, as well as a cumulative reduction in the need for SGCS.


Assuntos
Asma , Dermatite Atópica , Adulto , Masculino , Feminino , Humanos , Dermatite Atópica/tratamento farmacológico , Estudos Retrospectivos , Qualidade de Vida , Método Duplo-Cego , Asma/diagnóstico , Asma/tratamento farmacológico , Resultado do Tratamento , Índice de Gravidade de Doença
5.
Ter Arkh ; 95(1): 78-84, 2023 Feb 24.
Artigo em Russo | MEDLINE | ID: mdl-37167118

RESUMO

BACKGROUND: Primary immunodeficiencies (PIDs), now known as inborn errors of immunity, are a group of inherited diseases caused by defects in the genes that control the immune response. Patients with PIDs have risks of developing a severe course and/or death in COVID-19. Passive immunization with long-acting monoclonal antibodies (MABs) to SARS-CoV-2 should be considered as pre-exposure prophylaxis in patients with PIDs. Tixagevimab/cilgavimab is a combination of MABs that bind to the SARS-CoV-2 spike protein. AIM: To evaluate the efficacy and safety of pre-exposure prophylaxis of new SARS-CoV-2 infection in PIDs with the combination of tixagevimab/cilgavimab. MATERIALS AND METHODS: Forty eight patients diagnosed with PIDs were included in the study. Median follow-up after drug administration was 174 days. The total number of confirmed coronavirus infections in patients with PIDs as well as 6 months before and after administration of MAT were assessed. RESULTS: In the analyzed cohort, the overall incidence of COVID-19 from pandemic onset to MABs administration was 75% (36/48), with 31% (11/36) of over-infected patients having had the infection more than once. The incidence of COVID-19 immediately 6 months before the introduction of tixagevimab/cilgavimab was 40%. All patients who had COVID-19 after pre-exposure prophylaxis had a mild infection. The incidence of COVID-19 6 months after tixagevimab/cilgavimab administration significantly decreased compared to the incidence 6 months before administration (7 and 40%, respectively; p<0.001). CONCLUSION: The use of tixagevimab/cilgavimab in patients with PIDs is effective as pre-exposure prophylaxis and reduces the risk of severe COVID-19.


Assuntos
COVID-19 , Profilaxia Pré-Exposição , Humanos , Adulto , COVID-19/prevenção & controle , Moscou/epidemiologia , SARS-CoV-2 , Anticorpos Monoclonais
6.
Bull Exp Biol Med ; 173(6): 745-748, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36322313

RESUMO

In patients with chronic obstructive pulmonary disease, the levels of cytokines IL-1ß, IL-4, IL-8, TNFα, and IFNγ depended on the degree of bronchial obstruction and severity and period of the disease. The maximum levels of IL-4, IL-8, and TNFα were observed in severe chronic obstructive pulmonary disease during exacerbation. The highest concentration of IL-1ß and IFNγ were recorded during activation of inflammation in patients with moderate bronchial obstruction. The revealed correlations between the tested cytokines and spirometry parameters make it possible to consider the levels of these proteins as quantitative markers of systemic inflammation progression.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Fator de Necrose Tumoral alfa , Humanos , Citocinas , Inflamação , Interferon gama/genética , Interleucina-4 , Interleucina-8/genética , Fator de Necrose Tumoral alfa/genética
7.
Bull Exp Biol Med ; 173(6): 734-739, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36322302

RESUMO

IgM and IgG antibodies to the SARS-CoV-2 virus are detected in subjects who have recovered from COVID-19; IgM antibodies persist in a 1/3 of infected subjects up to 12 months from the moment of the disease, while IgG antibodies are present in the vast majority of cases (97%; medium and high levels antibodies were registered in 85% of cases). By the 12th month, 40% of those who recovered still have a very high level of IgG antibodies to the S-protein (>500 BAU/ml). In the feces, urine, and blood serum of patients with long-term persistent IgM antibodies, no coronavirus antigens were detected. After vaccination with the Gam-COVID-Vac vaccine, IgG antibodies to the S-protein are detected in 100% of cases and remain at a high level for 4 months, by the 5-6th month, the level of antibodies decreases. During revaccination, the level of IgG antibodies to S-protein reaches high values earlier than during primary vaccination, and remains high for 4 months (observation period). The blood sera of recovered and vaccinated patients have a high virus-neutralizing activity (at least 1:80), while its level is somewhat higher in recovered patients.


Assuntos
Anticorpos Antivirais , COVID-19 , Humanos , Imunização Secundária , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinação , Imunoglobulina M , Imunoglobulina G
8.
Ter Arkh ; 94(5): 675-682, 2022 Jun 17.
Artigo em Russo | MEDLINE | ID: mdl-36286968

RESUMO

BACKGROUND: The use of virus-neutralizing monoclonal antibodies is an effective method of etiotropic therapy for SARS-CoV-2 in patients of high-risk groups of severe COVID-19. Regdanvimab is a single-component monoclonal antibodies immunoglobulin G1, whose mechanism of action is aimed at binding SARS-CoV-2 virus at the RBD site of the spike protein S1 domain. In the Russian Federation, regdanvimab is approved for emergency administration in COVID-19 for adult patients not requiring respiratory therapy who are at high risk of developing a severe course of the disease. AIM: To evaluate the efficacy and safety of therapy with regdanvimab in patients with mild/moderate COVID-19 in a short-term hospital unit. MATERIALS AND METHODS: Virus-neutralizing therapy with regdanvimab was performed at the short-term hospital unit of the Moscow City Clinic. An open retrospective observational single-center study included 92 adult patients with mild/moderate coronavirus infection. All patients had comorbid chronic diseases and belonged to the high-risk group for the development of a severe COVID-19. INCLUSION CRITERIA: age 18 to 75 years; presence of a verified diagnosis of COVID-19 of mild/moderate COVID-19, polymerase chain reaction (PCR) confirmed; one or more chronic diseases; first 7 days from the onset of the first symptoms of COVID-19 (including day 7). EXCLUSION CRITERIA: need for oxygen support. Clinical efficacy was assessed according to the World Health Organization Сlinical Progression Scale and supplemented with laboratory markers at baseline and in dynamics, as well as with monitoring of virus elimination by PCR. STATISTICS: Calculations were performed using the statistical computing environment R 4.1.3 (R Foundation for Statistical Computing, Austria). For quantitative indices the median (1; 3 quartiles) was indicated. For binomial signs we calculated 95% confidence intervals according to Wilson's method. Time interval analysis was performed according to the KaplanMeier method. The significance level was determined at p0.05. RESULTS: A significant decrease in the severity of clinical manifestations according to the World Health Organization Clinical Progression Scale was noted by patients by day 4 after regdanvimab administration. All 92 patients in the cohort were discharged from the hospital l on average on day 5 after regdanvimab administration and on day 9 of the disease. On day 4 after drug administration 82% of patients was being PCR negative. No adverse events related to the administration of regdanvimab were reported during the study. CONCLUSION: In real clinical practice, the efficacy and safety of regdanvimab in patients at high risk of severe COVID-19 was confirmed once again, with a positive clinical result observed in a mixed cohort by the causative agent omicron and delta strain.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Adulto , Humanos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , COVID-19/epidemiologia , SARS-CoV-2 , Estudos Retrospectivos , Glicoproteína da Espícula de Coronavírus , Fatores de Tempo , Anticorpos Monoclonais Humanizados/efeitos adversos , Resultado do Tratamento , Oxigênio
9.
Bull Exp Biol Med ; 171(6): 736-740, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34705177

RESUMO

We studied the effect of tilorone on the dynamics of IFNα, IFNγ, and IL-1ß levels in the lung tissue and blood serum in relation to viral load in the lungs of BALB/c mice with pneumonia caused by influenza virus A/Aichi/2/68 (H3N2). Tilorone was administered per os in doses of 40, 150, and 540 µg per mouse 6, 30, and 78 h postinfection, which simulated the drug regimen used in the clinic for the treatment of influenza and acute respiratory viral infections in Russia and post-Soviet countries. Tilorone reduced viral load with the maximum amplitude (2-3 lg) after 1-2 administrations. The results of studying the dynamics of the cytokine levels in the infected animals in general support the previous hypothesis that, in repeated dosing, tilorone enhances the IFN response (compensates for its deficiency) at the early stages of acute respiratory viral infections and suppresses (damps) excessive production of IFN and proinflammatory cytokines at the later stages.


Assuntos
Antivirais/farmacologia , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Indutores de Interferon/farmacologia , Pulmão/efeitos dos fármacos , Infecções por Orthomyxoviridae/tratamento farmacológico , Tilorona/farmacologia , Animais , Esquema de Medicação , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Vírus da Influenza A Subtipo H3N2/crescimento & desenvolvimento , Vírus da Influenza A Subtipo H3N2/patogenicidade , Interferon-alfa/sangue , Interferon-alfa/imunologia , Interferon gama/sangue , Interferon gama/imunologia , Interleucina-1beta/sangue , Interleucina-1beta/imunologia , Pulmão/imunologia , Pulmão/virologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/sangue , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Carga Viral/efeitos dos fármacos
10.
Bull Exp Biol Med ; 171(2): 230-233, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34173107

RESUMO

The presence of IgG and IgM antibodies in the venous blood of 76 patients with confirmed COVID-19 infection was determined by ELISA using Russian test systems. Different levels of IgM antibodies to N-protein and receptor binding domain of the Spike protein (RBD) were revealed. The dynamics of IgG antibodies to the whole virion antigen and recombinant antigens showed high values on weeks 4-5 of the disease. The level of IgG antibodies to Nprotein remained low throughout the observation period. The characteristic dynamics of IgG measured using test systems with sorbed whole virion or recombinant spike proteins reflects the duration of the disease.


Assuntos
Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , COVID-19/diagnóstico , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Glicoproteína da Espícula de Coronavírus/imunologia , Antígenos Virais/genética , COVID-19/sangue , COVID-19/imunologia , COVID-19/virologia , Proteínas do Nucleocapsídeo de Coronavírus/genética , Ensaio de Imunoadsorção Enzimática , Humanos , Imunidade Humoral , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/genética , Fatores de Tempo , Vírion/genética , Vírion/imunologia
11.
Bull Exp Biol Med ; 170(6): 782-786, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33893966

RESUMO

We studied the effect of a combination of three muramylpeptides from gram-negative bacteria (Polymuramyl) on hematological parameters, morphology of the spleen, and serum cytokine level in mice with B16 melanoma treated with cyclophosphamide. Intraperitoneal administration of cyclophosphamide to tumor-bearing animals sharply reduced the number of leukocytes, especially neutrophils, in the blood and depleted the cellular composition of the spleen white pulp. Subsequent three daily intramuscular injections of Polymuramyl in doses of 70 and 860 ng/mouse for 3 days, as well as subcutaneous injection of the reference drug filgrastim (granulocytic CSF) in a dose of 12 µg/mouse partially corrected hematopoietic disorders and restored the cellular composition of the spleen. Granulocytic CSF more effectively replenished the content of mature neutrophils in the blood, while Polymuramyl restored the content of stab neutrophils. In contrast to granulocytic CSF, administration of Polymuramyl was followed by an increase in the level of granulocyte-macrophage CSF and a tendency to an increase in the serum content of IL-6, which indicates the involvement of these cytokines in the hematopoietic activity of Polymuramyl.


Assuntos
Ciclofosfamida/farmacologia , Fator Estimulador de Colônias de Granulócitos/metabolismo , Hematopoese/fisiologia , Animais , Interleucina-6/metabolismo , Masculino , Melanoma/metabolismo , Melanoma Experimental/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Baço/metabolismo
12.
Bull Exp Biol Med ; 170(5): 636-639, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33788112

RESUMO

The bactericidal activity of recombinant endolysins LysECD7, LysAm24, LysAp22, LysSi3 and LysSt11 was assayed in multidrug resistant strains (n=120) of Salmonella enterica, E. coli, Acinetobacter baumannii, Enterobacter spp., Pseudomonas aeruginosa, Klebsiella pneumoniae, and Campylobacter jejuni. The assay showed that the recombinant endolysins had a wide spectrum of bactericidal activity compared to endolysins of their progenitor phages. Among examined endolysins, we selected the active pharmaceutical substances with broad spectrum of bactericidal activity. Most strains were sensitive to LysECD7 (70.7%), LysAm24 (65%), and LysAp22 (58.6%), which seems to be promising causative agents for the development of finished dosage form.


Assuntos
Antibacterianos/farmacologia , Bacteriófagos/metabolismo , Endopeptidases/farmacologia , Acinetobacter baumannii/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla , Escherichia coli/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos
13.
Ter Arkh ; 93(1): 108-113, 2021 Jan 10.
Artigo em Russo | MEDLINE | ID: mdl-33720635

RESUMO

During a pandemic, nonspecific immunoprophylaxis of SARS-CoV-2 infection and other acute respiratory infections (ARI), which can worsen the course of COVID-19, is increasingly in demand in addition to specific immunization. BCG vaccine appears to be one of the candidate immunostimulants in this regard. At the same time, other microbe-derived preparations capable of inducing a state of trained immunity deserve attention. BCG and other bacterial immunostimulatory agents containing a large number of biologically active subunits have long been considered as objects of search for promising pharmacological substances. The review analyzes the linkages between BCG, mycobacterial adjuvants, bacterial lysates, trained immunity, muramylpeptides (MPs) and NOD2 receptors in light of the choice of a low molecular weight alternative to multicomponent bacterial immunostimulants for ARI prevention during the COVID-19 pandemic. The search for key molecules by which bacteria stimulate innate and adaptive immune responses proceeds in a spiral. On different loops of this spiral, MPs have repeatedly reproduced the nonspecific effects of multicomponent bacterial adjuvants, vaccines and immunostimulants. MPs and peptidoglycans containing MPs determine the adjuvant properties of the cell walls of mycobacteria and their peptide-glycolipid fraction (wax D). MPs were able to replace Mycobacterium tuberculosis in complete Freunds adjuvant. MPs determine the NOD2-dependent ability of BCG to induce trained immunity. Probably, MPs provide NOD2-mediated long-term prophylactic action of bacterial lysates. All of the above has prompted revisiting the previously obtained evidence of the efficacy of glucosaminylmuramyl dipeptide (GMDP) as a NOD2 agonist in treatment/prevention of respiratory infections. We speculate here that MPs, in particular GMDP, at rational dosing regimens will be able to reproduce many aspects of the nonspecific effects of BCG and multicomponent bacterial immunostimulants in preventing ARI during the COVID-19 pandemic and in the post-pandemic period.


Assuntos
COVID-19 , Pandemias , Vacina BCG , Extratos Celulares , Humanos , Imunidade Inata , Peso Molecular , SARS-CoV-2
14.
Klin Lab Diagn ; 66(7): 417-421, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34292684

RESUMO

The investigation aims - a quantitative assessment of cervical surface changes with digital analysis and computer technologies in dysplasia. Colposcopy was made in 90 women from 21 to 52 years (avr. age 33,9±8,13 y.o.) with mild epithelial dysplasia (CIN1), moderate dysplasia (CIN2), severe dysplasia (CIN3). The algorithm detected indicators which provide the cervical dysplasia classification on pre cytological and pre molecular-genetic patients investigations. The outcome of an algorithm was the identification of the cervix surface condition severity by an objective quantification. The cervical dysplasia type (CIN) was classified as IndGV values. The mild dysplasia (CIN1) had IndGV=8,5, moderate dysplasia (CIN2) - IndGV=13, severe dysplasia (CIN3) - IndGV=15,6. The cervical affected surface area (IndInt) equalled 0,17 in CIN1, 0,19 in CIN2, 0,22 in CIN3. A change severity has a direct relation with a grey color value. It demonstrates quantify classification in digital analysis. The algorithm is used in real-time mode and no requires considerable material outlays. This makes it possible to use an algorithm after clinical examination and predict patient management.


Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Adulto , Colposcopia , Feminino , Humanos , Hiperplasia , Gravidez , Displasia do Colo do Útero/diagnóstico
15.
Bull Exp Biol Med ; 169(1): 95-99, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32495165

RESUMO

We studied changes in the transcription of genes encoding cytokines (TNF, IL-6, IL-10, and IL-32), cell activation markers (ICAM1, CD38, Fas, and FCGRIII), ROS production catalyst (NOX2), autophagy (Beclin 1, LC3B, and p62) and apoptosis (BAX, BCL2) regulators in peripheral blood mononuclear cells upon contact with quantum dots CdSe/ZnS-MPA and CdSe/CdSeZnS/ZnS-PTVP. Up-regulation of TNF, ICAM1, Fas, p62 mRNA and down-regulation of the FCGRIII and NOX2 mRNA in response to the presence of quantum dots were revealed. The formation of serum protein corona on the surface of quantum dots abolished this effect.


Assuntos
Inflamação/genética , Leucócitos Mononucleares/efeitos dos fármacos , Coroa de Proteína/química , Pontos Quânticos , Adulto , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Compostos de Cádmio/farmacologia , Compostos de Cádmio/toxicidade , Citocinas/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Mediadores da Inflamação/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Pontos Quânticos/química , Pontos Quânticos/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Compostos de Selênio/farmacologia , Compostos de Selênio/toxicidade , Compostos de Zinco/farmacologia , Compostos de Zinco/toxicidade
16.
Bull Exp Biol Med ; 168(6): 748-752, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32328936

RESUMO

Pharmacokinetics of suppository forms of bacteriophages was studied on male Chinchilla rabbits. Suppositories with various composition of bacteriophages were administered once per rectum to rabbits, and the presence of phage particles was estimated in the blood, urine, and feces over 24 h. Pharmacokinetic study showed that the phages were detected in the blood, urine, and feces at various terms of the experiment irrespective of the size of viral particles, which confirmed the possibility of their systemic effects after rectal administration. Thus, the use of suppository form of bacteriophages can ensure the presence of phage particles even in infection foci that cannot directly contact with the preparation.


Assuntos
Bacteriófagos/isolamento & purificação , DNA Viral , Fezes/virologia , Administração Retal , Animais , Bacteriófagos/metabolismo , Disponibilidade Biológica , DNA Viral/sangue , DNA Viral/urina , Masculino , Coelhos , Supositórios/administração & dosagem
17.
Ter Arkh ; 92(12): 195-200, 2020 Dec 15.
Artigo em Russo | MEDLINE | ID: mdl-33720594

RESUMO

It has long been known that Bacillus CalmetteGurin (BCG) vaccine provides nonspecific protection against many non-mycobacterial infections, which has been discussed in the last decade through the prism of the concept of trained immunity. Within the framework of this concept, a persistent increase in resistance to various pathogens, which occurs after an infectious disease or exposure to certain microbial agents, is associated with epigenetic reprogramming of innate immune cells and their bone marrow progenitors. The COVID-19 pandemic has drawn attention of scientists and practitioners to BCG as an inducer of trained immunity. A number of epidemiological studies have suggested a negative association between the coverage of the population with BCG vaccination and the burden of SARS-CoV-2 infection. A series of independent clinical studies of the effectiveness of this vaccine in non-specific prevention of COVID-19 has been initiated in different countries. Recently, the key role of cytosolic NOD2 receptors in BCG-induced trained immunity has been proven. This actualizes the search for effective immunoactive preparations for prevention of respiratory infections in the pandemic among low molecular weight peptidoglycan fragments of the bacterial cell wall, muramylpeptides (MPs), which are known to be NOD2 agonists. The review highlights the proven and proposed linkages between BCG, MPs, NOD2 and trained immunity in the light of the COVID-19 pandemic. Analysis of the data presented indicates the prospects for preclinical and clinical studies of MPs as potential drugs for nonspecific prevention of SARS-CoV-2 infection and/or other respiratory infections in risk groups during the pandemic. First of all, attention should be paid to glucosaminylmuramyl dipeptide, approved for clinical use in Russia and a number of post-Soviet countries for the complex treatment and prevention of acute and recurrent respiratory infections.


Assuntos
Bacillus , COVID-19 , Vacina BCG , Humanos , Imunidade Inata , Pandemias , Federação Russa , SARS-CoV-2
18.
Klin Lab Diagn ; 65(7): 443-453, 2020 Jun 04.
Artigo em Russo | MEDLINE | ID: mdl-32762184

RESUMO

The aim of the work - to establish the interconnection and interdependence of toll-like mediated pathogenetic mechanisms of urogenital infection in pregnant women from the position of epigenomics. Using discriminant analysis in 89 patients with urogenital infection in pregnant women for the first time was established a reliable evidence-based relationship and interdependence between mucosal immunity, the severity of the infectious process, clinical manifestations, symptoms of miscarriage in the background of simultaneous development of the infectious process and pregnancy. For urgent delivery (infection), urgent childbirth (infection and clinical manifestation) and premature birth, mucosal immunity determines the severity of anti-infective resistance (with increasing mucosal immunity oppression of infectious process and clinical manifestations is logged , and its decrease increases the severity of infection process and clinical manifestations); the inhibition of mucosal immunity prevails over its hyperreaction (inhibition of mucosal immunity is determined by the physiological immunodepression in response to the development of pregnancy, as well as in response to herpes virus infection when activated); the severity of the infectious process depends on the severity of clinical manifestations and symptoms of miscarriage. During miscarriage mucosal immunity provides the pathophysiological course of infectious process and the clinical manifestations and development of symptoms of misacrriage; increasing levels of mucosal immunity to hyperreaction contributes to the development of symptoms of abortion and miscarriage; not registered mutual influence of oppression, mucosal immunity and its hyperreaction; the severity of the infectious process does not depend on the severity of clinical signs and symptoms of miscarriage. In urgent childbirth (infection), the oppression of mucosal immunity does not affect the severity of clinical manifestations, symptoms of abortion and the infectious process. In urgent or premature birth, and termination of pregnancy, the oppression of mucosal immunity affects the severity of clinical manifestations, the severity of the infectious process and the symptoms of abortion; the severity of clinical manifestations and the severity of the symptoms of abortion are interrelated. In urgent birth (infection) mucosal immunity overreaction affects the severity of clinical manifestations, symptoms of miscarriage and infection; in case of term and preterm labour overreaction mucosal immunity on the severity of infection and symptoms of abortion and does not affect the severity of clinical manifestations and at the termination of a pregnancy mucosal immunity on the severity of the infectious process and does not affect the severity of clinical signs and symptoms of abortion. The levels of mucosal immunity inhibition, its hyperreaction, clinical manifestations, symptoms of pregnancy termination and the severity of the infectious process do not depend on the type of herpes simplex virus. In the absence of infection with herpes simplex virus in patients with urogenital infections of pregnant women, there is no mutual influence and the relationship between the oppression of mucosal immunity and hyperreaction of mucosal immunity, the oppression of mucosal immunity prevails over its hyperreaction. With increasing mucosal immunity oppression, increased anti-infectious resistance of the body (the decreased activity of the infectious process), and with its decrease decreased (increased activity of the infectious process). Hyperreaction of mucosal immunity influenced the severity of pregnancy termination symptoms, clinical manifestations and infectious process, and also determined the severity of pregnancy termination symptoms. The severity of the infectious process and clinical manifestations influenced the symptoms of abortion. The severity of the infectious process did not affect the clinical manifestations. During infection with herpes simplex virus type I or type I and II on the background prevalence of oppression mucosal immunity over hyperreaction mucosal immunity, the presence of relationships between them, and the impact of mucosal immunity on the severity of the infectious process and the clinical manifestations increase mucosal immunity has been shown to decrease the severity of infection and clinical manifestations (reduction of anti-infective resistance), while reducing mucosal immunity the severity of infection and clinical manifestations increased. Hyperreaction of mucosal immunity influenced the severity of pregnancy termination symptoms and determined the severity of pregnancy termination symptoms. The severity of the infectious process and clinical manifestations influenced the symptoms of abortion. The severity of clinical manifestations reflects the severity of the infectious process. In type I and type II of pregnancy, the level of mucosal immunity determines the anti-infectious resistance of the body in urogenital infection of pregnant women. Inhibition of mucosal immunity and its hyperreactions are interrelated, have an impact on each other, as a result of their integral interaction, increasing the levels of mucosal immunity leads to a decrease in the severity of clinical manifestations and the infectious process, reducing the levels of mucosal immunity contributes to the manifestation of clinical manifestations, as well as increasing the severity of the infectious process. Hyperreaction of mucosal immunity affects the severity of symptoms of abortion, infection and clinical manifestations. The infectious process and clinical manifestations determine the severity of the symptoms of abortion. In type III and type IV of pregnancy course, there is no mutual influence of mucosal immunity oppression and its hyperreaction. The levels of indicators of mucosal immunity oppression and its hyperreaction are interrelated; the increase in the severity of mucosal immunity oppression is accompanied by a decrease in clinical manifestations and severity of the infectious process and vice versa. Hyperreaction of mucosal immunity affects the severity of symptoms of abortion, infection and clinical manifestations. The infectious process determines the severity of the symptoms of abortion and clinical manifestations, acting as a leading component of gestational complications in urogenital infection of pregnant women. In the III type of pregnancy course oppression of mucosal immunity does not affect the severity of symptoms of miscarriage. In the IV type of pregnancy course, the levels of mucosal immunity oppression prevail over the indicators of mucosal immunity hyperreaction, which is due to the integral interaction of physiological inhibition of immunological reactivity of the organism in response to pregnancy and inhibition of immunological reactivity of the organism, accompanying the activation of infectious process of viral genesis. Hyperreaction of mucosal immunity determines the symptoms of abortion.


Assuntos
Aborto Espontâneo , Trabalho de Parto Prematuro , Complicações Infecciosas na Gravidez , Complicações na Gravidez , Nascimento Prematuro , Aborto Espontâneo/genética , Análise Discriminante , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/genética
19.
Bull Exp Biol Med ; 166(6): 754-758, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31028579

RESUMO

We studied immunocorrecting effects of Semax (Met-Glu-His-Phe-Pro-Gly-Pro) on the model of "social" stress caused by sensory contact and intermale confrontation. Functional activity of the immune system of laboratory animals was evaluated in standard immunopharmacological tests: delayed-type hypersensitivity reaction, direct agglutination test, latex test for studying phagocytic activity of peripheral blood neutrophils, changes in differential leukocyte count, and weight of immunocompetent organs. It was found that changes in the immune response caused by "social" stress are multidirectional, which confirms the theory of stress-induced "immune imbalance". Semax acted as effective immune corrector restoring cellular and humoral immunogenesis reactions and phagocytic activity of neutrophils. This attested to the presence of immunomodulating properties in Semax and necessitates further studies in this field.


Assuntos
Hormônio Adrenocorticotrópico/análogos & derivados , Fatores Imunológicos/farmacologia , Fármacos Neuroprotetores/farmacologia , Nootrópicos/farmacologia , Fragmentos de Peptídeos/farmacologia , Estresse Psicológico/tratamento farmacológico , Hormônio Adrenocorticotrópico/farmacologia , Agressão , Animais , Animais não Endogâmicos , Hipersensibilidade Tardia/tratamento farmacológico , Hipersensibilidade Tardia/imunologia , Imunidade Inata/efeitos dos fármacos , Testes de Fixação do Látex , Contagem de Leucócitos , Masculino , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Fagocitose/efeitos dos fármacos , Estresse Psicológico/imunologia , Estresse Psicológico/fisiopatologia
20.
Bull Exp Biol Med ; 168(1): 58-61, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31768778

RESUMO

We studied antibacterial activity of a hybrid polymeric construction consisting of continuous and porous layers of ultrahigh-molecular-weight polyethylene reinforced by titanium. Experimental samples were impregnated with amoxycillin in subcritical Freon R22. The contact of bacterial culture with hybrid polymeric constructions saturated with amoxycillin suppressed the growth of microorganisms and the formation of their colonies. These results attest to the presence of a bactericidal effect of hybrid scaffold samples impregnated with an antibacterial component.


Assuntos
Antibacterianos/química , Polietilenos/química , Polímeros/química , Alicerces Teciduais/química , Amoxicilina/química , Porosidade
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