Резюме. В настоящее время в литературе активно обсуждается неоднозначная роль распознаю-щих рецепторов врожденного иммунитета, в частности TLRs, в иммунопатогенезе бронхиальной астмы (БА).Цель нашей работы -исследование экспрессии ТLR2 и TLR4 на уровне клеток слизистой полости носа и лейкоцитов периферической крови (ЛПК) больных БА разной степени тяжести.В исследование были включены 40 детей с БА (3-12 лет) и 10 здоровых детей того же возраста. Методом ПЦР-РВ оценивали экспрессию генов TLR2 и TLR4 в соскобах со слизистой полости носа и в ЛПК; методом проточной цитометрии определяли процент моноцитов, лимфоцитов и гранулоци-тов, экспрессирующих TLR2 TLR4, и интенсивность их экспрессии; методом мультиплексного им-мунофлуоресцентного анализа оценивали уровень про-и противовоспалительных цитокинов (IL-1β, IL-1ra, IL-6, IL-8, IL-10, TNFα) в назальных смывах.В результате проведенного исследования выявлена гиперактивация факторов врожденного имму-нитета на уровне слизистой оболочки полости носа у больных с БА, проявляющаяся повышением экспрессии генов TLR2, TLR4 и выработки как провоспалительных, так и противовоспалительных цитокинов. Выявлена связь между уровнем цитокинов и степенью тяжести бронхиальной астмы. В периферической крови определено достоверное увеличение экспрессии TLR2 и TLR4 на циркули-рующих CD14 + моноцитах у детей с БА. Таким образом, показано увеличение экспрессии генов TLRs слизистой полости носа и повыше-ние поверхностной экспрессии TLR2 и TLR4 на циркулирующих моноцитах больных бронхиальной астмой по сравнению со здоровыми детьми. Выявленные изменения свидетельствуют о вовлечении системы TLRs в иммунопатогенез бронхиальной астмы. В дальнейшем TLRs могут быть использова-ны в качестве маркеров прогноза течения БА и возможных терапевтических мишеней.
The experimental group included 68 children over 6 years of age who had recovered from COVID-19. The control group included 22 children over 6 years of age who have never had COVID-19. Research methods included neurological examination, verification of cognitive status, examination by an otolaryngologist, and smell and taste assessment. The examination was performed 6–8 weeks after COVID-19 recovery and after 1 year in some patients. Children who recovered from COVID-19 had a reduction in their ability to smell compared to children who had never had COVID-19. The olfactory thresholds and taste identification scores after recovery from COVID-19 were identical, whether the parents had reported anosmia in their children during COVID-19 or not, and irrespective of hyperthermia level and the presence or absence of headache and hyperhidrosis during COVID-19. Analysis of correlation with neuropsychiatric symptoms showed no differences in the olfactory thresholds in children irrespective of the presence of neuropsychiatric symptoms (tics, tremors, enuresis, compulsive movements, seizures, speech disorders, attention deficit, and easy fatigability) both in general, and in particular among subjects performing or not any compulsive movements, and experiencing or not a combination of easy fatigability and daytime sleepiness. Evidence suggests that in children and adolescents, partial hyposmia is associated with depressive symptoms, varying in severity from low to high, but symptoms of depression were not caused by COVID-19 infection itself. Analysis in subgroups with different degrees of state and trait anxiety did not reveal any significant differences in the olfactory threshold. A re-examination of 21 children was performed after 1 year. An objective olfactometric examination showed that the sensitivity to odorants increased significantly. In 1 year, we compared the thresholds of smell in children who had COVID-19 and those who did not have this disease: olfactory sensitivity after COVID-19 in children is restored to normal values. Schulte correction test showed that none of 14 children with asthenic manifestations in the form of fluctuations or exhaustion when performing the test immediately after COVID-19 had these manifestations after 1 year. Thus, asthenization of cognitive activity was recorded within the next 1.5 months after suffering from COVID-19 but was absent after 1 year.
Федеральное государственное автономное образовательное учреждение высшего образования «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Министерства здравоохранения Российской Федерации, 117990, г. Москва, Российская Федерация 2 Научно-исследовательский институт педиатрии и охраны здоровья детей Федерального государственного бюджетного учреждения «Центральная клиническая больница Российской академии наук» Министерства науки и высшего образования Российской Федерации, 119333, г. Москва, Российская Федерация РезюмеВведение. COVID-19 -тяжелое респираторное заболевание, вызванное β-коронавирусом SARS-CoV-2, которое характеризуется иммуноопосредованным повреждением тканей и органов. Доказано, что у детей заболевание протекает относительно легко по сравнению со взрослыми и механизмы врожденного иммунитета играют в этом важную роль.Цель исследования -изучение экспрессии генов, кодирующих рецепторы врожденного иммунитета TLR4, TLR7, а также анализ изменения экспрессии провоспалительных цитокинов: интерлейкина(ИЛ)-1β, фактора некроза опухолей (ФНО)α и интерферона(ИФН)-α -на уровне гена и белка у детей с COVID-19 в зависимости от тяжести течения заболевания.Материал и методы. В исследование включены 55 детей с подтвержденным диагнозом COVID-19. Группы пациентов формировали на основании жалоб и клинических проявлений. 1-я группа детей с бессимптомным течением включала 9 человек. Во 2-ю группу входили дети с легкой формой течения -36 человек, в 3-ю группусо среднетяжелой формой течения (10 человек). Группу сравнения составили 25 здоровых детей. Из полученного материала выделяли РНК и методом полимеразной цепной реакции в реальном времени определяли уровень экспрессии генов, а также методом мультиплексного иммунофлуоресцентного анализа определяли уровень содержания цитокинов в надосадочной жидкости.Результаты. Показано статистически достоверное увеличение экспрессии генов рецепторов врожденного иммунитета (TLR4, TLR7) в клетках слизистой оболочки ротоглотки у детей с COVID-19. Экспрессия TLR4 и TLR7 была, соответственно, в 2,6 и 7,2 раза выше у детей со среднетяжелым течением по сравнению с группой здоровых. Вместе с этим выявлено повышение уровня экспрессии провоспалительных цитокинов (ИЛ-1β, ФНОα, ИФН-α) на уровне гена и белка, ассоциированное с тяжестью течения COVID-19. Также было показано увеличение продукции хемокинов, которое коррелировало с тяжестью течения заболевания.Обсуждение. Увеличение уровня экспрессии генов TLR4 и TLR7 клетками слизистой ротоглотки у детей с COVID-19 указывает на их роль в патогенезе заболевания. Основная функция TLR4 и TLR7 заключается в распознавании патоген-ассоциированных молекулярных паттернов, а именно гликопротеина шипа, участвующего в проникновении вируса в клетки-мишени и одноцепочечной РНК вируса. Активация TLR4 и TLR7 приводит к Toll-индуцируемой экспрессии генов провоспалительных цитокинов (ИЛ-1β, ФНОα, ИФН-α) и хемокинов, достоверное увеличение экспрессии генов и продукции белка которых были нами продемонстрированы. Это играет огромную роль в ...
The issue of recurrent upper respiratory tract diseases in children is common and relevant. Commonly this pathology is associated with other diseases that lead to the prolonged, complicated, or chronic course of the inflammatory process in the upper respiratory tract. Objective. The aim of the study is to improve management principles for children with recurrent upper respiratory tract diseases according to the developed multidisciplinary and personalized approach (modern methods of diagnosis and health monitoring) for achieving long-term remission. Methods. The study included 65 children aged from 3 to 17 years 11 months with recurrent upper respiratory tract diseases. Examination: nasal, nasopharynx and larynx endoscopy, abdominal ultrasound with aqueous-siphon test, tympanometry, and laboratory tests (complete blood count, evaluation of total and specific IgE levels, antistreptolysin O, nasopharynx and oropharynx microbiological study, enzyme-linked immunosorbent fecal analysis for Helicobacter pylori). Results. 88% of examined children showed allergic pathology according to our study results. Clinical signs of gastroesophageal reflux disease (GERD) were revealed in 30% of children with chronic oropharynx inflammation. GERD signs were revealed both via abdominal ultrasound with aqueous-siphon test and via fiberoptic laryngoscopy and later confirmed by esophagogastroscopy in 8.7% of patients. Obtained data indicates high prevalence of allergic and gastroenterological pathology in children with recurrent upper respiratory tract diseases. Conclusion. Obtained results allow us to establish scientifically multidisciplinary and personalized approach for the management of children with recurrent upper respiratory tract disease. This approach shall include key diagnostic methods required for improvement of comorbid conditions revealing, and achieving and maintaining control over the disease symptoms. The study is currently ongoing.
Background. The role of recently discovered neurospecific peptides in the pathogenesis of acute and progressive neurologic disorders, their neuroprotective features, and possibilities to use them as markers for the course and prognosis of certain diseases have been actively studied in recent decades. However, neurospecific peptides are almost not studied in chronic residual diseases. In our study we measured the levels of neurospecific peptides and some other markers to achieve understanding of general neurophysiological trends in congenital and acquired chronic non-progressive brain pathology with reference to the selection of relevant groups — study objects. Objective. The aim of the study is to study patterns of neurospecific peptides, neurotransmitters and neuroreceptor markers distribution in the serum of children with various pathogenetic variants of chronic neuropathology. Methods. The study included children from 3 to 16 years old with different pathologies. The sample was divided into groups by pathology type: no sensory and neurological disorders, congenital sensory deficit due to mutation of genes expressed and not expressed in the brain, early acquired sensory deficit of multifactorial nature, congenital mild and severe organic disorders of central nervous system (CNS) in residual stage without baseline sensory deficit, acquired functional CNS disorders without baseline organic defect and sensory deficit. The following laboratory data (neurophysiological components) was studied: nerve growth factor, brain-derived neurotropic factor, neurotrophin-3, neurotrophin-4, neuregulin-1-beta-1, beta-secretase, sirtuin-1, synaptophysin, neuronal nitric oxide synthase, and anti-NR2 glutamate receptor antibodies. The parameters of cognitive activity, sense of vision, sense of smell, and acoustic sense were also evaluated. Results. The study included 274 participants. Neuropeptides and markers have shown a variable degree and range in the group spectrum of differences from normal levels. The most variable in the examined sample was NO-synthase, as well as levels of both neurotrophins, beta-secretase, and glutamate receptor marker. All visual deficits were associated with increased NO-synthase levels (p < 0.001). Neuroplasticity peptides (beta-secretase, neurotrophin-3 and 4) have been activated in all pathological conditions. Nerve growth factor and brain-derived neurotropic factor were specifically activated in mild organic CNS lesions (mild cognitive impairments), while neuregulin — in congenital genetically determined visual deficits. There was no specific activation of neuropeptides and NO-synthase level tended to decrease in cases of severe CNS lesions. Conclusion. The study results suggest that all types of early visual impairment are associated with increased physiological neuronal activity, and non-organic neurological functional disorders — mainly with increased physiological synaptic activity. General neuroplasticity processes were activated in all cases of visual deficits but more specific. However, more specific and well-studied processes were activated in mild organic CNS lesions, and neuroplasticity processes did not activate adequately in severe organic CNS lesions probably due to the limited neuronal and synaptic resources.
The number of criminal cases against doctors has increased in recent years. The major reason for them was failure in delivery of any medical services that resulted in harm to health or death of the patient. The legislation of the Russian Federation for the medical industry is imperfect, however, the health care delivery failure can be associated with doctors’ non-compliance to the action algorithms specified by regulatory acts. The review has collected up-to-date legislative information regarding polypharmacy, off-label drug administration, irrational antibiotic therapy, that are neglected by doctors. Although, these problems become more and more crucial and they arouse interest of investigation bodies.
At the present time, the role of innate immunity in pathogenesis of bronchial asthma (BA) is actively studied, in particular, significance of TLRs and cytokines. The study included 42 patients with severe bronchial asthma (from 3 to 12 years old), and 67 healthy children at the same age. Expression of TLR2, TLR4, and TLR9 genes was evaluated by PCR-RT from the scrapings of nasal mucosa; cytokines (IL-33, TSLP, IL-4, TGF-β1 and IL-28B) were assayed in nasal swabs by ELISA technique. The main results were as follows: an increased gene expression of TLR2, TLR4, TLR9 genes was revealed in the nasal mucosa scraps from the patients with bronchial asthma as compared to healthy children. We have also measured the contents of important cytokines secreted by the respiratory epithelium in the course of TLRs activation. The study of IL-33, TSLP, IL-4 in nasal samples revealed significantly increased concentrations of these cytokines in the patients with severe BA against the control group. A study of TGF-βlevels in nasal cavity swabs revealed a significant decrease of this regulatory cytokine in the group of pediatric patients with asthma. Worth of note, evaluation of antiviral IL-28B cytokine in the group of patients with severe BA showed a significant downward trend, in comparison to the control indexes. Hence, one may conclude on some disturbances of local innate immunity system in the patients with severe BA which manifest as hyperexpression of TLRs genes, increased production of proinflammatory and epithelial cytokines, decreased production of antiviral IL-28B cytokine, and TGF-β1.
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