Natural chain-breaking antioxidants and their synthetic analogs as modulators of oxidative stress

Oxidative stress is associated with the increased production of reactive oxygen species or with a significant decrease in the effectiveness of antioxidant enzymes and nonenzymatic defense. The penetration of oxygen and free radicals in the hydrophobic interior of biological membranes initiates radical disintegration of the hydrocarbon “tails” of the lipids. This process is known as “lipid peroxidation”, and the accumulation of the oxidation products as peroxides and the alde-hydes and acids derived from them are often used as a measure of oxidative stress levels. In total, 40 phenolic antioxidants were selected for a comparative study and analysis of their chain-breaking antioxidant activity, and thus as modulators of oxidative stress. This included natural and natural-like ortho-methoxy and ortho-hydroxy phenols, nine of them newly synthesized. Applied experimental and theoretical methods (bulk lipid autoxidation, chemiluminescence, in silico methods such as density functional theory (DFT) and quantitative structure–activity relationship ((Q)SAR) modeling) were used to clarify their structure–activity relationship. Kinetics of non-inhibited and inhibited lipid oxidation in close connection with inhibitor transformation under oxidative stress is considered. Special attention has been paid to chemical reactions resulting in the initiation of free radicals, a key stage of oxidative stress. Effects of substituents in the side chains and in the phenolic ring of hydroxylated phenols and biphenols, and the concentration were discussed

SYNTHESIS OF ALKID FILM-FILTERS MODIFIED BY FATTY ACIDS OF TALL OIL

Formulations of new alkyd resins using tall oil fatty acids have been developed, as well as a technology for their production under laboratory conditions. Alkyd film formers modified with fatty acids of tall oil were synthesized

Особенности ведения пациентов с хронической обструктивной болезнью легких на фоне отказа от табакокурения: фокус – на оптимизацию поддерживающей терапии

The aim of this study was to investigate effects of stepping down the dose of inhaled steroid (ICS) or ICS withdrawal in patients with chronic obstructive pulmonary disease (COPD) treated with an adequate bronchodilating therapy and quitting smoking. Methods. The study was performed in real clinical settings. Patients with COPD (n = 41) involved in educational smoking cessation program were followed for 9 months in outpatient settings. Smoking cessation program included varenicline, adequate physical activity, nutritional counseling and bronchodilating therapy; one of the aims of the treatment was ICS dose reduction or complete withdrawal of ICS. Results. Long-acting beta-2-agonist (LABA) indacaterol and dual bronchodilators (indacaterol/glycopyrronium or indacaterol/tiotropium) were effective in patients with COPD quitting tobacco smoking. ICS dose was reduced more quickly in patients treated with indacaterol or dual bronchodilators compared to those treated with formoterol. Quitting smoking was associated with improvement in CAT score and reduction in COPD exacerbation rate. Conclusion. Treatment with indacaterol or indacaterol/glycopyrronium combination was associated with more rapid and safe stepping down the dose of ICS or ICS withdrawal in COPD patients quitting tobacco smoking compared to those treated with formoterol.Табакокурение (ТК) является основным модифицируемым фактором риска развития хронической обструктивной болезни легких (ХОБЛ). При отказе от ТК в 1-ю неделю происходит усиление бронхообструктивного синдрома, что может являться одной из причин возобновления курения. Материалы и методы. На базе кабинета по отказу от ТК Санкт-Петербургского государственного бюджетного учреждения здравоохранения «Городская поликлиника № 54» в условиях реальной амбулаторной практики проходили обучение пациенты с ХОБЛ (n = 41). Наблюдение осуществлялось в амбулаторных условиях через 3 и 9 мес. от начала исследования. Отказ от ТК осуществлялся при использовании варениклина на фоне адекватной физической активности, рационального питания и подбора бронхолитической терапии ХОБЛ; при этом одной из задач являлось снижение дозы и отмена терапии ингаляционными глюкокортикостероидами (иГКС). Результаты. По данным исследования продемонстрированы эффективность адекватной базисной терапии бронходилататорами длительного действия на фоне отказа от ТК у пациентов с ХОБЛ и возможность снижения дозы или полной отмены иГКС. При этом отмечена стабилизация респираторного статуса и гемодинамических показателей. Подтверждена эффективность применения длительно действующего β2-агониста (ДДБА) индакатерола, а также двойной комбинации индакатерола и длительно действующих антихолинергических препаратов (гликопирроний или тиотропий) как основы базисной терапии у пациентов с ХОБЛ в период отказа от ТК. Заключение. Продемонстрирована возможность более быстрого достоверного снижения дозы или полной отмены терапии иГКС у пациентов, получавших индакатерол в период отказа от ТК, по сравнению с лицами, принимавшими другой ДДБА – формотерол. Показано преимущество применения индакатерола, особенно в сочетании с гликопирронием

In vitro biotization

In vitro coculture of plant tissue explants with beneficial microorganisms enhance their tolerance to abiotic and biotic stresses. The induced resistance response caused by the inoculants is referred to as “biotization”. There is enough experimental evidence with bacteria (bacterization) and vesicular arbuscular mycorrhiza (mycorrhization) inoculations to recommend utilization of this technology in commercial micropropagation. Micropropagated plantlets usually exhibit high mortality rate upon their transfer to soil, so biotization technique can improve survival and is considered to be a perspective method in clonal micropropagation

Polymorphism of the clinical manifestations of progressive mitochondrial encephalomyopathy associated with POLG1 gene mutation

The common cause of mitochondrial diseases is mutations in the POLG1 gene encoding the catalytic subunit of DNA-polymerase gamma that is responsible for the replication and repair of mitochondrial DNA. Diseases associated with POLG1 gene defects are characterized by obvious clinical polymorphism and may resemble some mitochondrial syndromes and other hereditary and nonhereditary diseases, which gives rise to diagnostic difficulties. Another characteristic feature is that phenotypic manifestations are of diversity in various patients having the same mutation in the POLG1 gene. The paper describes mitochondrial encephalomyopathy, caused by homozygous mutation in the polymerase gamma (POLG1, p.L304R), with different clinical manifestations and a poor outcome in patients from two different families

Biopterin-deficient hyperphenylalaninemia: Diagnosis and treatment

The term phenylketonuria encompasses some genetically heterogeneous diseases from a group of hereditary amino acid metabolic disorders, the key biochemical sign of which is a steady increase in blood phenylalanine levels – hyperphenylalaninemia. Phenylketonuria is a most common disease of the above group; its rate in the Russian Federation is 1:7140 neonates. The rare causes of hyperphenylalaninemia include the cofactor (biopterin-deficient) forms associated with tetrahydrobiopterin deficiency, leading to the blocked metabolic pathways for converting phenylalanine to tyrosine and for synthesizing catecholamine and serotonin precursors (L-dopa and 5-hydroxytryptophan). The distinguishing feature of all cofactor forms of hyperphenylalaninemia is the inefficiency of an isolated low-protein diet. Cofactor therapy with sapropterin in combination with correction of neuromediatory disorders is used in the combination treatment of these patients. The paper presents a case history of a child with severe biopterin-deficient hyperphenylalaninemia resulting from a defect in the PTS gene. The clinical example illustrates difficulties associated with the diagnosis of cofactor hyperphenylalaninemia and with long individual dosage adjustments for medications

Immune-mediated epilepsies in children

The paper reviews the current literature on immune-mediated pediatric epilepsies. It describes the clinical picture, laboratory diagnosis, and treatment of autoimmune encephalitides (limbic encephalitis and anti-NMDA-receptor antibody encephalitis), Hashimoto's encephalopathy, opsoclonus-myoclonus-syndrome, and Rasmussen's syndrome, as well as groups of acute encephalopathies with immune-mediated status epilepticus (FIRES-, DESK-, HHE- syndrome). A clinical case of Hashimoto's encephalopathy is described. Emphasis is laid on a close relationship between epilepsy and inflammation, including the development of an autoimmune process due to recurrent epileptic seizures

Specific features of the clinical and laboratory diagnosis of Lesch—Nyhan syndrome and current therapy options

The rare hereditary diseases encountered in the practice of pediatricians, pediatric neurologists, and geneticists include Lesch—Nyhan syndrome associated with purine metabolic disorders caused by mutations in the HPRT1 gene encoding the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). HGPRT deficiency gives rise to hyperuricemia, hyperuricemic nephropathy, and a CNS lesion reminiscent of dystonic or hyperkinetic infantile cerebral paralysis concurrent with a propensity to have autoaggressive behavior. The diagnosis is based on a range of history data, characteristic neurological symptoms, the detection of high blood and urine uric acid levels, and the identification of pathogenic mutagens in the HPRT1 gene. Early diagnosis contributes to timely therapy and assists in medical genetic counseling. The paper describes a clinical case of a boy with Lesch-Nyhan syndrome and elucidates the problems of diagnosis and treatment of this disease

IXa glycogenosis – diagnosis, features of clinical manifestations and treatment

IXa glycogenosis is the most common of the currently known 15 types of glycogenosis. The disease has X-linked recessive inheritance, is caused by mutations in  the PHKA2 gene localized on the short arm of X chromosome in  the Хр22.13 region. The main manifestations of the disease: stunted growth, increased liver size, episodes of hypoglycemia, fasting ketosis, increased blood levels of cholesterol, low-density lipoproteins, triglycerides, liver transaminases. In many cases, the course of the disease can be relatively mild, which complicates early diagnosis and the timely administration of therapy. Clinical observations of two children from unrelated families with the same homozygous c.884G> A mutation (р.Arg295His, or R295H) in the PHKA2 gene are presented. The similarities and differences in clinical symptoms are emphasized, and the features of patient management are presented

Influence of Nicotine from Diverse Delivery Tools on the Autonomic Nervous and Hormonal Systems

Background: Through measurements of the heart rate variability (HRV) accompanied by the pertinent biomarker assays, the effects of nicotine and byproducts derived from alternative nicotine delivery systems (ANDS) on the autonomic nervous system (ANS) and hormonal system have been investigated. Methods: HRV was studied in a group of volunteers (17 people), involving non-smokers, i.e., who never smoked before (11), ex-smokers (4) and active smokers (2). ANDS and smoking simulators, including regular, nicotine-free and electronic cigarettes; tobacco heating systems; chewing gums and nicotine packs of oral fixation (nic-packs), were used. Blood pressure, levels of stress hormones in saliva and catecholamines in the blood were also monitored. Results: HRV analysis showed relatively small changes in HRV and in the other studied parameters with the systemic use of nic-packs with low and moderate nicotine contents (up to 6 mg) compared to other ANDS. Conclusions: The HRV method is proven to be a promising technique for evaluation of the risks associated with smoking, dual use of various ANDS and studying the biomedical aspects of smoking cessation. Nic-packs are shown to be leaders in biological safety among the studied ANDS. A sharp surge in the activity of the sympathetic division of the ANS within the first minutes of the use of nicotine packs implies that nicotine begins to act already at very low doses (before entering the blood physically in any significant amount) through fast signal transmission to the brain from the nicotinic and taste buds located in the mouth area