Functional nitric oxide conjugate systems state/restored heart thiols of rats in modeling isadrine-pituitrin’s myocardial infarction using metabolite-tropic cardioprotector “Angiolin”

Background: According to modern researches, endothelial dysfunction (ED) is one of the primary pathogenetic elements of cardiovascular diseases (myocardial infarction [MI], ischemic heart diseases, cerebral ischemic stroke, atherosclerosis, arterial hypertension, pulmonary hypertension, heart failure, and dilated cardiomyopathy) as well as obesity, hyperlipidemia, diabetes and hyperhomocysteinemia. The aim of this work was to study the influence of potential metabolitotropic cardioprotector “Angiolin” on the parameters of conjugate systems nitric oxide (NO)/restored thiols in heart under isadrine-pituitrin MI.Methods: This study was performed on Wistar white rats weighing 190-210 g. Biochemical, immune-enzyme analysis and histoimmunechemical study were performed.Results: In histological sections of hearts of the rats receiving Angiolin in parenteral dosing 50 mg/kg 30 mins before each pituitrin injection the density of endothelial NO-synthase (NOS)-positive cells increased by 29% and the density of inducible NOS-positive cells decreased by 23.3%. In cytosolic fraction of myocardium homogenate NOS activity increased by 27%, the concentration of NO stable metabolites increased by 70% and the content of nitrosative stress marker nitrotyrosine decreased by 42% when compared with control group. At the same time in similar samples of heart homogenate the increase of restored thiol groups’ level by 53.3%, methionine - by 35.1%, cysteine - by 170% and activity of glutathione reductase - by 186% was noted. The administration of reference drug mildronate to the animals with MI in dose 100 mg/kg did not result in significant changes of the studied parameters of thiol-disulfide system and NO system of the heart when compared with control group.Conclusions: Angiolin does not influence directly on NOS in MI, but at the same time protects NO from nitrosative stress increasing restored equivalents of thiol-disulfide system

Современные подходы к ведению детей с гипофосфатазией

Hypophosphatasia is rare genetic disease caused by tissue-nonspecific alkaline phosphatase deficiency due to the mutation in the ALPL gene. Disease can manifest in utero, in childhood or in adults depending on its form and severity. This article presents modern data on the epidemiology, etiology, and clinical signs of hypophosphatasia in children, covers in details differential diagnostic search, and gives guidelines for its evidence-based treatment. Without timely treatment the prognosis of the disease is unfavorable in most cases. Such patients require follow-up by multidisciplinary team of physicians. The only effective method of treatment is enzyme replacement therapy with asfotase alfa. Symptomatic therapy is also crucial as well as physiotherapeutic procedures and therapeutic exercise programs (at rehabilitation stage).Гипофосфатазия — редкое генетическое заболевание, обусловленное дефицитом тканенеспецифической щелочной фосфатазы в результате мутации в гене ALPL. В зависимости от формы и тяжести болезнь может дебютировать внутриутробно, в детском возрасте или у взрослых. В статье представлены современные сведения об эпидемиологии, этиологии и клинических проявлениях гипофосфатазии у детей, подробно освещаются этапы дифференциально-диагностического поиска, приведены рекомендации по лечению, основанные на принципах доказательной медицины. При отсутствии своевременного лечения прогноз болезни в большинстве случаев неблагоприятный для жизни. Пациенты нуждаются в наблюдении мультидисциплинарной командой врачей. Единственным эффективным методом лечения является ферментозаместительная терапия асфотазой альфа; необходимо также проводить симптоматическую терапию, а при реабилитации пациентов использовать физиотерапевтические процедуры и лечебные физкультурные комплексы упражнений