МИТОХОНДРИАЛЬНАЯ ДИСФУНКЦИЯ У ДЕТЕЙ С ПЕЧЕНОЧНЫМИ ФОРМАМИ ГЛИКОГЕНОВОЙ БОЛЕЗНИ

Aim: The purpose of the study was to assess mitochondrial dysfunction severity in patients with hepatic forms of glycogen storage disease (GSD). Patients and methods: We examined 53 children with GSD in the dynamics. Distribution of children by disease types was: 1st group — children with GSD type I, 2nd group — children with GSD type III, 3rd group — children with GSD type VI and IX; comparison group consisted of 34 healthy children. Intracellular dehydrogenases activity: succinate dehydrogenase (SDH), glycerol-3-phosphate-dehydrogenase (GPDH),nicotinamideadenin-Н-dehydrogenase (NADH-D) and lactatdehydrogenase (LDH) was measured using the quantitative cytochemical method in the peripheral lymphocytes. Results: It was revealed decrease of SDH- (р 0.001) and GPDH-activities (р 0.001), along with increase of the NADH-D activity (р 0.05) in all patients with GSD, (SDH / NADH-D) index was decreased (р 0.001). LDH activity was increased in groups 1 (р 0.05) and 3 (p 0.01), compared with comparison group. The most pronounced intracellular enzymes activity deviations were observed in children with GSD type I, that correspond to more severe clinical form of GSD. It was found strong correlation between intracellular enzymes activity and both hepatomegaly level (R =0.867) and metabolic acidosis severity (R =0.987). Conclusion: Our investigation revealed features of mitochondrial dysfunction in children with GSD, depending on the GSD type. Activities of lymphocytes enzymes correlates with the main disease severity parameters and can be used as an additional diagnostic criteria in children with hepatic form of GSD.Цель исследования: оценить характер митохондриальных дисфункций у детей с печеночными формами гликогеновой болезни (ГБ). Пациенты и методы: в динамике обследовано 53 ребенка с ГБ, которые в зависимости от типа заболевания были распределены на 3 группы: 1-я — дети с ГБ типа I; 2-я — с ГБ типа III; 3-я — с ГБ типа VI и IX. Группу сравнения составили 34 условно здоровых ребенка. Активность внутриклеточных дегидрогеназ: сукцинатдегидрогеназы (СДГ), глицерол-3-фосфатдегидрогеназы (ГФДГ), никотинамидаденин-Н-дегидрогеназы (НАДН-Д) и лактатдегидрогеназы (ЛДГ) определяли количественным цитохимическим методом в лимфоцитах периферической крови. Результаты: обнаружено снижение активности СДГ (р 0,001) и ГФДГ (р 0,001) на фоне повышения активности НАДН-Д (р 0,05), а также снижение индекса СДГ / НАДН-Д (р 0,001) у всех пациентов c ГБ. Активность ЛДГ по отношению к группе сравнения была повышена в 1-й (р 0,05) и 3-й (p 0,01) группе. Наиболее выраженные изменения активности внутриклеточных дегидрогеназ имели место у детей с ГБ типа I, что соответствует более тяжелому клиническому течению данной формы патологии. Установлено, что активность внутриклеточных дегидрогеназ лимфоцитов сильно коррелирует с выраженностью гепатомегалии (R =0,86) и степенью метаболического ацидоза (R =0,987). Выводы: у детей с печеночными формами ГБ обнаружены признаки митохондриальной дисфункции, степень выраженности которых зависит от типа заболевания. Активность ферментов лимфоцитов коррелирует с основными параметрами оценки тяжести состояния, что позволяет использовать данные показатели в качестве дополнительных диагностических критериев у детей с ГБ.

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

EFFECT OF INTRAVENOUS CONTRAST MEDIA ON LYMPHOCYTE ENERGY CYCLE ENZYMES IN CHILDREN WITH RENAL AND URINARY TRACT DISEASES

The effect of contrast media used for intravenous pyelography onto intracellular energy cycle ensymes was investigated. All types of nonionic contrast media inhibited succinatdehydrogenase and alfa-glycerophosphatdehydrogenase. This inhibition was less pronounced with Iodixanol injection. The way to prevent this metabolic changes is proposed and tested.Key words: Contrast media, intravenous pyelography, children

EFFECT OF INTRAVENOUS CONTRAST MEDIA ON LYMPHOCYTE ENERGY CYCLE ENZYMES IN CHILDREN WITH RENAL AND URINARY TRACT DISEASES

The effect of contrast media used for intravenous pyelography onto intracellular energy cycle ensymes was investigated. All types of nonionic contrast media inhibited succinatdehydrogenase and alfa-glycerophosphatdehydrogenase. This inhibition was less pronounced with Iodixanol injection. The way to prevent this metabolic changes is proposed and tested.Key words: Contrast media, intravenous pyelography, children

INFORMATIVE ENERGY EXCHANGE OF PERIPHERAL LYMPHOCYTE BLOOD MITOCHONDRIA IN CHILDREN WITH CHRONIC CONSTIPATION

The article discusses the study of cell metabolism condition in chronic constipation children based on the activities of the two mitochondrion enzymes, succinate dehydrogenate and glycerophosphate dehydrogenase detected in cytochemical analysis of blood lymphocytes over the light microscope. The study involved 79 children and proved that in children with chronic constipation the activity of both dehydrogenases goes down, which demonstrates the apparent reduction of energy exchange of blood lymphocyte mitochondria. The correlation analysis showed that the duration of chronic constipation and the associated changes in the large intestine negatively affect the energy processes in cells. Thus the longer the pathology goes on, the smaller the energy exchange in mitochondria is resulting in reduced compensatory abilities in the body.Key words: children, chronic constipation, succinate dehydrogenase of blood lymphocytes, diagnostics

ВЛИЯНИЕ РЕНТГЕНОКОНТРАСТНЫХ ПРЕПАРАТОВ НА АКТИВНОСТЬ ФЕРМЕНТОВ ЭНЕРГЕТИЧЕСКОГО ОБМЕНА ЛИМФОЦИТОВ У ДЕТЕЙ С НЕФРОУРОЛОГИЧЕСКОЙ ПАТОЛОГИЕЙ

The effect of contrast media used for intravenous pyelography onto intracellular energy cycle ensymes was investigated. All types of nonionic contrast media inhibited succinatdehydrogenase and alfa-glycerophosphatdehydrogenase. This inhibition was less pronounced with Iodixanol injection. The way to prevent this metabolic changes is proposed and tested.Key words: Contrast media, intravenous pyelography, children.Исследовано влияние различных рентгеноконтрастных препаратов, используемых для рентгеноурографических обследований у детей, на активность внутриклеточных ферментов энергетического обмена — сукцинатдегидрогеназы и -глицерофосфатдегидрогеназы лимфоцитов. Выявлено угнетающее влияние всех исследованных рентгено-контрастных препаратов на энергетический обмен лимфоцитов, с минимальным проявлением эффекта торможения ферментной активности у йодиксанола. Предложена схема коррекции метаболических нарушений, вызываемых рентгеноконтрастными препаратами. Ключевые слова: рентгеноконтрастные препараты, рентгеноурография, дети. (Педиатрическая фармакология. – 2009;6(6): 66-69