Функциональное состояние митохондрий лимфоцитов периферической крови при черепно-мозговой травме у детей

Backgraund: It is known that mitochondria play an important role in the mechanisms of brain cells damage and death following traumatic brain injury (TBI). However, the relationship between the severity of brain damage following TBI and mitochondrial dysfunction are not well defined. Aim: to study activities of NADN- and succinate dehydrogenases, a key enzyme of mitochondrial oxidative phosphorylation in children with TBI of varying severity and different outcomes; to detect ATP content in lymphocytes; the level of NOx and 3-nitrotyrosine in serum and plasma. Methods: all parameters were determined in the dynamics of one month following TBI, and in some cases up to the death of patients. The severity of TBI was scored by Glasgow Coma Scale (GCS), the outcome of TBI — Glasgow Outcome Scale (GOS). Based on the clinical examination children with TBI were divided into 3 groups: (1) mild TBI; (2) severe TBI and (3) severe TBI with fatal outcome. Results: we found that activity of dehydrogenases is significantly reduced only in patients with the poor neurologic outcome. The greatest decrease in these parameters was observed in patients with severe traumatic brain injury and fatal outcome. A direct correlation was found between the indices of dehydrogenases activity and ATP content in lymphocytes (r =0.97, p =0.005). The levels of NOx metabolites and 3-nitrotyrosine were significantly increased in children with severe TBI. Conclusion: obtained results suggest that mitochondrial dysfunction, impaired cerebral energy metabolism and oxidative stress contribute to cell death in the brain and thus represent therapeutic targets for the treatment of TBI.Обоснование. Известна важная роль митохондрий в механизмах повреждения и гибели клеток мозга при черепно-мозговой травме (ЧМТ). Однако вопросы взаимоотношений между тяжестью повреждения мозга при ЧМТ и митохондриальной дисфункцией окончательно не решены. Цель исследования: определить активность NADH- и сукцинатдегидрогеназ —ключевых ферментов окислительного фосфорилирования митохондрий; содержание аденозинтрифосфата в лимфоцитах при ЧМТ; уровень NOx и 3-нитротирозина в периферической крови у детей, перенесших травмы различной степени тяжести и имеющих разные исходы ЧМТ. Материалы и методы: определение указанных показателей проводилось в динамике до одного месяца, а в отдельных случаях — вплоть до гибели больных. Тяжесть ЧМТ оценивали в баллах по шкале комы Глазго, исход ЧМТ — по шкале исходов Глазго. Детей с ЧМТ на основании клинической оценки разделили на 3 группы — с легкой, тяжелой и с тяжелой ЧМТ и летальным исходом. Результаты: исследования показали, что активность дегидрогеназ достоверно снижалась только у больных с тяжелой ЧМТ и неблагоприятным исходом. Наибольшее снижение этих показателей выявлено у больных с летальным исходом. Обнаружена прямая корреляционная зависимость между показателями активности дегидрогеназ и содержанием аденозинтрифосфата в лимфоцитах (r =0,97, p =0,005). Содержание метаболитов NOx у детей с тяжелой ЧМТ на порядок превышало их уровень у здоровых детей и больных с легкой ЧМТ. Уровень 3-нитротирозина в плазме крови был тем выше, чем тяжелее была ЧМТ. Заключение. Обнаруженные при ЧМТ у детей митохондриальная дисфункция, нарушение мозгового энергетического обмена и окислительный стресс могут приводить к повреждению и гибели клеток мозга, а также быть мишенями для адекватной терапии ЧМТ

COMPARATIVE EVALUATION OF THE ADEQUACY OF ANESTHESIA WITH XENON AND SEVOFLURANE IN CHILDREN SURGERY

Xenon have been used as an anesthetic in the Russian Federation for 11 years in anesthesia in adult patients. In April 2010, the permission of the Ministry of Health and Social Development for the clinical studies evaluating the efficacy and safety of medical xenon anesthesia in children based on the Institute of Emergency Children’s Surgery and Traumatology had been received. Xenon in pediatric anesthesiology is of a special interest because it has properties equivalent to an «ideal anesthetic». To assess its effectiveness in anesthesia in children 42 patients aged 1 to 18 years were included in the study. A comparative assessment of the adequacy of anesthesia with xenon and sevoflurane has been conducted. At different stages of the research in addition to clinical parameters the level of growth hormone and cortisol were measured. The study showed that anesthesia with xenon was different from sevoflurane by hemodynamic stability, and both have a high level of anesthetic anti-stress activity. Key words: anesthesia with xenon, stress hormones, anesthesia in children. (Pediatric pharmacology. — 2011; 8 (6): 77–81)

COMPARATIVE EVALUATION OF THE ADEQUACY OF ANESTHESIA WITH XENON AND SEVOFLURANE IN CHILDREN SURGERY

Xenon have been used as an anesthetic in the Russian Federation for 11 years in anesthesia in adult patients. In April 2010, the permission of the Ministry of Health and Social Development for the clinical studies evaluating the efficacy and safety of medical xenon anesthesia in children based on the Institute of Emergency Children’s Surgery and Traumatology had been received. Xenon in pediatric anesthesiology is of a special interest because it has properties equivalent to an «ideal anesthetic». To assess its effectiveness in anesthesia in children 42 patients aged 1 to 18 years were included in the study. A comparative assessment of the adequacy of anesthesia with xenon and sevoflurane has been conducted. At different stages of the research in addition to clinical parameters the level of growth hormone and cortisol were measured. The study showed that anesthesia with xenon was different from sevoflurane by hemodynamic stability, and both have a high level of anesthetic anti-stress activity. Key words: anesthesia with xenon, stress hormones, anesthesia in children. (Pediatric pharmacology. — 2011; 8 (6): 77–81)

RENIN ANGIOTENSIN SYSTEM GENE POLYMORPHISMS IN CHILDREN WITH NEPHROTIC SYNDROM

To investigate the role of the reninangiotensin system genes polymorphisms in develop and progression of nephrotic syndrom (NS) in children we determined the genotypes of angiotensin converting enzyme (ACE), angiotensinogen (AGT) and angiotensin ii receptor (ATII-R) of 1 type in 80 russian children with ns including and 15 children with chronic renal failure (CRF). Genotype frequencies did not differ between patients with ns and controls (n = 165). The distribution of ace, AGT and ATII-R 1 type genotypes was similar among ns sub groups, such as focal segmental glomerulosclerosis (FSGS) (n = 18), steroid-sensitive nephrotic syndrome (n = 32), nephrotic syndrome with hypertension and hemoturia (n = 22) and with control group. When ns subjects with CRF (n = 15) were compared with control, the prevalence of ace DD genotype was significantly higher (47% VS 21%; χ2 = 4,44; p < 0,05). Our results indicate that the DD genotype ace may be a factor of risk for the dеvеlopment of progressive renal impairment in the children with nephrotic syndrome. The analysis of treatment's effect with inhibitor of ace in groups patients with steroid resistant NS (SRNS) demonstrated decreasing of renoprotective effect of this drugs in patients with id and dd genotypes com? Pared with ii genotype: the degree of blood pressure, proteinuria and the rate of glomerular filtration decrease was significantly lower (55,46 ± 9,25 VS 92,74 ± 25; р < 0,05) in these patients.Key words: nephrotic syndrom, chronic renal failure, polymorphism of genes, renin-angiotensin system

RENIN ANGIOTENSIN SYSTEM GENE POLYMORPHISMS IN CHILDREN WITH NEPHROTIC SYNDROM

To investigate the role of the reninangiotensin system genes polymorphisms in develop and progression of nephrotic syndrom (NS) in children we determined the genotypes of angiotensin converting enzyme (ACE), angiotensinogen (AGT) and angiotensin ii receptor (ATII-R) of 1 type in 80 russian children with ns including and 15 children with chronic renal failure (CRF). Genotype frequencies did not differ between patients with ns and controls (n = 165). The distribution of ace, AGT and ATII-R 1 type genotypes was similar among ns sub groups, such as focal segmental glomerulosclerosis (FSGS) (n = 18), steroid-sensitive nephrotic syndrome (n = 32), nephrotic syndrome with hypertension and hemoturia (n = 22) and with control group. When ns subjects with CRF (n = 15) were compared with control, the prevalence of ace DD genotype was significantly higher (47% VS 21%; χ2 = 4,44; p < 0,05). Our results indicate that the DD genotype ace may be a factor of risk for the dеvеlopment of progressive renal impairment in the children with nephrotic syndrome. The analysis of treatment's effect with inhibitor of ace in groups patients with steroid resistant NS (SRNS) demonstrated decreasing of renoprotective effect of this drugs in patients with id and dd genotypes com? Pared with ii genotype: the degree of blood pressure, proteinuria and the rate of glomerular filtration decrease was significantly lower (55,46 ± 9,25 VS 92,74 ± 25; р < 0,05) in these patients.Key words: nephrotic syndrom, chronic renal failure, polymorphism of genes, renin-angiotensin system

ANGIOTENSIN CONVERTING ENZIME GENE I/D POLYMORPHISM AND PROMISSING OF RENOPROTECTIVE AND IMMUNOSUPRESSIVE THERAPY IN CHILDREN WITH NEPHROTIC SYNDROME

To investigate the role of i/d polymorphism gene angiotensin converting enzyme (ACE) in promissing of renoprotective and immunosupressive therapy in children with nephrotic syndrome syndrome (NS) we determined the genotypes of ACE in 76 children with ns including 22 children with chronic renal failure (CRF). the analysis of treatment effect with inhibitor ace in patients with steroid resistant ns (SRNS) demonstrated decreasing of renoprotective effect of these drugs in patients with DD genotype compared with ii and id genotypes (р = 0,033) by similar degree of the glomerular filtration rate (GFR), proteinuria and blood pressure decrease in these patients. Percentage of DD genotype in patients with ns refractory to therapy of cyclosporin a were height compared with patients, sensitive to this therapy.Key words: nephrotic syndrome, chronic renal failure, polymorphism of genes, renin-angiotensin system

ANGIOTENSIN CONVERTING ENZIME GENE I/D POLYMORPHISM AND PROMISSING OF RENOPROTECTIVE AND IMMUNOSUPRESSIVE THERAPY IN CHILDREN WITH NEPHROTIC SYNDROME

To investigate the role of i/d polymorphism gene angiotensin converting enzyme (ACE) in promissing of renoprotective and immunosupressive therapy in children with nephrotic syndrome syndrome (NS) we determined the genotypes of ACE in 76 children with ns including 22 children with chronic renal failure (CRF). the analysis of treatment effect with inhibitor ace in patients with steroid resistant ns (SRNS) demonstrated decreasing of renoprotective effect of these drugs in patients with DD genotype compared with ii and id genotypes (р = 0,033) by similar degree of the glomerular filtration rate (GFR), proteinuria and blood pressure decrease in these patients. Percentage of DD genotype in patients with ns refractory to therapy of cyclosporin a were height compared with patients, sensitive to this therapy.Key words: nephrotic syndrome, chronic renal failure, polymorphism of genes, renin-angiotensin system

GENETIC FOUNDATIONS OF THE BRONCHIAL ASTHMA

The article overviews the results of the studies of the genetic foundations of predisposition to the bronchial asthma. The authors provide detailed information on the molecular and genetic mechanisms of the bronchial asthma, roles performed by the polymorphisms of the interleukin genes and their receptors, IgE receptors, adrenergic receptors, CYS-LT enzymes in the pathogenesis of this disease, as well as their impact on the effectiveness of the drug therapy.Key words: bronchial asthma, genetic predisposition, pharmacogenetics

EXPERIENCE OF TREATMENT WITH IBANDRONIC ACID IN PATIENTS WITH SEVERE RHEUMATOLOGICAL DISEASES AND SYSTEMIC OSTEOPOROSIS

This article presents the results of a study of effectiveness and safety of ibandronic acid in 21 children with rheumatologic diseases and severe systemic osteoporosis. The treatment with ibandronic acid during 48 weeks provided statistically significant increase of mineral density of bones, decrease of pain intensity, lessening of serum concentration of bone resorption marker — C-terminal telopeptide. The development of repeated compressive fractures of vertebrae and bones of peripheral skeleton at the time of treatment with this medication was not detected. Key words: children, rheumatological diseases, osteoporosis, treatment, bifosfonates, ibandronic acid.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(1):116-121

СРАВНИТЕЛЬНАЯ ОЦЕНКА АДЕКВАТНОСТИ АНЕСТЕЗИИ КСЕНОНОМ И СЕВОФЛУРАНОМ У ДЕТЕЙ В ПЛАНОВОЙ ХИРУРГИИ

Xenon have been used as an anesthetic in the Russian Federation for 11 years in anesthesia in adult patients. In April 2010, the permission of the Ministry of Health and Social Development for the clinical studies evaluating the efficacy and safety of medical xenon anesthesia in children based on the Institute of Emergency Children’s Surgery and Traumatology had been received. Xenon in pediatric anesthesiology is of a special interest because it has properties equivalent to an «ideal anesthetic». To assess its effectiveness in anesthesia in children 42 patients aged 1 to 18 years were included in the study. A comparative assessment of the adequacy of anesthesia with xenon and sevoflurane has been conducted. At different stages of the research in addition to clinical parameters the level of growth hormone and cortisol were measured. The study showed that anesthesia with xenon was different from sevoflurane by hemodynamic stability, and both have a high level of anesthetic anti-stress activity. Key words: anesthesia with xenon, stress hormones, anesthesia in children. (Pediatric pharmacology. — 2011; 8 (6): 77–81).На территории Российской Федерации в течение 11 лет при анастезии у взрослых пациентов в качестве анестетика используется ксенон. В апреле 2010 г. получено разрешение Минздравсоцразвития РФ на проведение клинических исследований по оценке эффективности и безопасности медицинского ксенона при анестезиях у детей на базе НИИ неотложной детской хирургии и травматологии. К ксенону в детской анестезиологии проявляется особый интерес, поскольку он по своим свойствам приравнивается к «идеальному анестетику». Для оценки его эффективности при анестезиях у детей в исследование были включены 42 пациента в возрасте от 1 года до 18 лет. Проводилась сравнительная оценка адекватности анестезии ксеноном и севофлураном. На разных этапах исследования помимо клинических показателей определялся уровень соматотропного гормона и кортизола. Исследование показало, что анестезия с использованием ксенона отличается от анестезии севофлураном гемодинамической стабильностью, при этом оба анестетика обладают высоким уровнем антистрессорной активности. Ключевые слова: анестезия ксеноном, гормоны стресса, анестезия у детей. (Педиатрическая фармакология. — 2011; 8 (6): 77–81)