Применение липофлавона в комплексном лечении хронических обструктивных заболеваний легких

Применение липофлавона в комплексном лечении хронических обструктивных заболеваний легки

Catalytic Function of PLA2G6 Is Impaired by Mutations Associated with Infantile Neuroaxonal Dystrophy but Not Dystonia-Parkinsonism

Mutations in the PLA2G6 gene have been identified in autosomal recessive neurodegenerative diseases classified as infantile neuroaxonal dystrophy (INAD), neurodegeneration with brain iron accumulation (NBIA), and dystonia-parkinsonism. These clinical syndromes display two significantly different disease phenotypes. NBIA and INAD are very similar, involving widespread neurodegeneration that begins within the first 1-2 years of life. In contrast, patients with dystonia-parkinsonism present with a parkinsonian movement disorder beginning at 15 to 30 years of age. The PLA2G6 gene encodes the PLA2G6 enzyme, also known as group VIA calcium-independent phospholipase A(2), which has previously been shown to hydrolyze the sn-2 acyl chain of phospholipids, generating free fatty acids and lysophospholipids.We produced purified recombinant wildtype (WT) and mutant human PLA2G6 proteins and examined their catalytic function using in vitro assays with radiolabeled lipid substrates. We find that human PLA2G6 enzyme hydrolyzes both phospholipids and lysophospholipids, releasing free fatty acids. Mutations associated with different disease phenotypes have different effects on catalytic activity. Mutations associated with INAD/NBIA cause loss of enzyme activity, with mutant proteins exhibiting less than 20% of the specific activity of WT protein in both lysophospholipase and phospholipase assays. In contrast, mutations associated with dystonia-parkinsonism do not impair catalytic activity, and two mutations produce a significant increase in specific activity for phospholipid but not lysophospholipid substrates.These results indicate that different alterations in PLA2G6 function produce the different disease phenotypes of NBIA/INAD and dystonia-parkinsonism. INAD/NBIA is caused by loss of the ability of PLA2G6 to catalyze fatty acid release from phospholipids, which predicts accumulation of PLA2G6 phospholipid substrates and provides a mechanistic explanation for the accumulation of membranes in neuroaxonal spheroids previously observed in histopathological studies of INAD/NBIA. In contrast, dystonia-parkinsonism mutations do not appear to directly impair catalytic function, but may modify substrate preferences or regulatory mechanisms for PLA2G6

Usage of lipoflavon in the treatment of chronic obstructive pulmonary diseases

Особые надежды на решение проблемы ХОЗЛ связывают с разработкой новых перспективных направлений базисной терапии «цитокинассоциированных» воспалительных заболеваний, включающих использование лекарственных средств с антицитокиновой активностью. Необходимо также учитывать, что негативные «пульмогенные» эффекты главного этиологического фактора ХОЗЛ – табакокурения, во многом реализуются через стимуляцию синтеза провоспалительных цитокинов. Цель. Дать научное обоснование целесообразности использования липофлавона для коррекции цитокинового гомеостаза в комплексном лечении тяжелых форм хронического обструктивного заболевания легких у лиц с длительным стажем табакокурения.Settlement of COPD problem is associated with the development of new perspective ways of basic therapy “cytokine-associated” inflammatory diseases, including the using of drugs with anticytokine activity. It is necessary to take into account that negative “pulmogenic” effects of the main etiological factor of COPD - smoking is largely realizated through the stimulation of synthesis of proinflammatory cytokines. The aim of investigation: to motivate an expediency of lipoflavon application in the complex treatment of severe forms of chronic obstructive pulmonary disease in individuals with long period of smoking for the correction of cytokine homeostasis