Correlation between Antioxidant Enzymes Activity and Intraerythrocyte Concentration of Fe, Mg, Zn, Cu in Pulmonary Arterial Hypertension and Cor Pulmonale in Children with Congenital Lung Disease and Cystic Fibrosis

Significant changes in the levels of the potential prooxidant Cu (increase) and the antioxidant Zn (decrease) in plasma were revealed in children having bronchopulmonary dysplasia (BPD) complicated by pulmonary arterial hypertension (PAH) and chronic cor pulmonale (CCP) when compared with the control. The Zn / Cu ratio in the blood plasma of patients with BPD, especially in CCP, was found to be lower than in the control group (p<0.001). This could indicate the activation of the prooxidant processes; simultaneously, the total antioxidant status (AOS) decreased. No significant increase in the intracellular free (“ionized” (i)) form of magnesium (iMg) was found; in fact, the concentration of iFe in all the patient groups was higher than in the control. An increase in the iCu and iZn levels (nonprotein-bound) was observed in the blood cells of the affected children. A significant increase in the glutathione peroxidase activity in the CCP patients may indicate an accumulation of organic peroxides, and partially compensate for the lesser activity of superoxide dismutase (SOD) and other antioxidants. The Zn / Cu and iZn/ iCu ratios were reduced in patients with CCP when compared with patients with PD without CCP

LINE-1 retrotransposon methylation in chorionic villi of first trimester miscarriages with aneuploidy

Purpose High frequency of aneuploidy in meiosis and cleavage stage coincides with waves of epigenetic genome reprogramming that may indicate a possible association between epigenetic mechanisms and aneuploidy occurrence. This study aimed to assess the methylation level of the long interspersed repeat element 1 (LINE-1) retrotransposon in chorionic villi of first trimester miscarriages with a normal karyotype and aneuploidy. Methods The methylation level was assessed at 19 LINE-1 promoter CpG sites in chorionic villi of 141 miscarriages with trisomy of chromosomes 2, 6, 8-10, 13-15, 16, 18, 20-22, and monosomy X using massive parallel sequencing. Results The LINE-1 methylation level was elevated statistically significant in chorionic villi of miscarriages with both trisomy (45.2 +/- 4.3%) and monosomy X (46.9 +/- 4.2%) compared with that in induced abortions (40.0 +/- 2.4%) (p < 0.00001). The LINE-1 methylation levels were specific for miscarriages with different aneuploidies and significantly increased in miscarriages with trisomies 8, 14, and 18 and monosomy X (p < 0.05). The LINE-1 methylation level increased with gestational age both for group of miscarriages regardless of karyotype (R = 0.21, p = 0.012) and specifically for miscarriages with trisomy 16 (R = 0.48, p = 0.007). LINE-1 methylation decreased with maternal age in miscarriages with a normal karyotype (R = - 0.31, p = 0.029) and with trisomy 21 (R = - 0.64, p = 0.024) and increased with paternal age for miscarriages with trisomy 16 (R = 0.38, p = 0.048) and monosomy X (R = 0.73, p = 0.003). Conclusion Our results indicate that the pathogenic effects of aneuploidy in human embryogenesis can be supplemented with significant epigenetic changes in the repetitive sequences

ФАКТОРЫ РИСКА СЕРДЕЧНО-СОСУДИСТЫХ ЗАБОЛЕВАНИЙ И ЦЕНТРАЛЬНОЙ ГЕМОДИНАМИКИ У СТУДЕНТОВ-СТАРШЕКУРСНИКОВ

HighlightsThe article examines the prevalence of risk factors for cardiovascular diseases (CVD) and the state of central hemodynamics (CHD) in senior students. Aim. To study the risk factors for CHD and CVD in senior students with the aim of early detection of arterial hypertension (AH) and the implementation of therapeutic and prophylactic measures.Methods. The study involved 223 senior students of medical universities in Moscow aged 20-27 years (the mean age was 22.8±0.17 years). The following cardiovascular risk factors were assessed for each student: age, gender, smoking, physical activity, genetic predispositions; body mass index. The indicators of CHD were studied by volumetric compression oscillometry using a portable automated software-hardware complex for non-invasive research of central hemodynamics (“SHCNIR CHD vco-“Globus” device).Results. The presence of CVD risk factors in senior students was revealed in 52.5% of cases; more than two risk factors were found in 19.3% of cases; 1st degree arterial hypertension (AH) in 11.2% of cases; “white coat hypertension” in 10.8% of cases; genetic predisposition to CVD in 30.0% of cases; overweight in 17.0% of cases; obesity in 5.4% of cases; low physical activity in 23.8% of cases; smoking in 16.1% of cases. An altered CHD profile was found in 62.1% of students. An increase in total peripheral vascular resistance at normal blood pressure levels was noted in 31.8% of cases. Indicators of total peripheral vascular resistance, mean blood pressure, systolic and diastolic blood pressure were significantly higher in the group of students with CHD risk factors.Conclusion. Outpatient follow-up groups should include students with established risk factors for cardiovascular diseases, diagnosed AH, and with altered indicators of CHD. Preventive examinations should include a simple method for studying hemodynamics – compression oscillometry.Основные положенияВ статье исследованы частота факторов риска развития сердечно-сосудистых заболеваний и состояние центральной гемодинамики у студентов старших курсов. Цель. Изучить основные факторы риска сердечно-сосудистых заболеваний (ФР ССЗ) и центральной гемодинамики (ЦГД) у студентов-старшекурсников.Материалы и методы. Обследованы 223 студента старших курсов медицинских вузов Москвы в возрасте 20–27 лет (средний возраст составил 22,8±0,17 года). У каждого студента оценены основные ФР ССЗ: возраст, пол, курение, физическая активность, наследственность, индекс массы тела. Показатели ЦГД исследованы методом объемной компрессионной осциллометрии с помощью портативного автоматизированного программно-аппаратного комплекса неинвазивного исследования центральной гемодинамики (прибор «КАП ЦГ осм-«Глобус»).Результаты. ФР ССЗ выявлены у 52,5% студентов старших курсов, более двух факторов риска обнаружено у 19,3%. Артериальная гипертензия I степени зарегистрирована у 11,2% лиц, артериальная гипертензия «белого халата» – у 10,8%, отягощенная наследственность – у 30,0%, избыточная масса тела – у 17,0%, ожирение – у 5,4%, гиподинамия – у 3,8%, курение – у 16,1% обследованных. Измененный профиль ЦГД обнаружен у 62,1% студентов. Повышение общего периферического сосудистого сопротивления при нормальных уровнях артериального давления определено у 31,8% лиц. Показатели общего периферического сосудистого сопротивления, среднего, систолического и диастолического артериального давления были достоверно выше в группе студентов с ФР ССЗ.Заключение. В группу диспансерного наблюдения необходимо включать студентов не только с установленными ФР ССЗ, выявленной артериальной гипертензией, но и измененными показателями ЦГД. В профилактические осмотры необходимо добавить простой метод исследования гемодинамики – компрессионную осциллометрию

Preferentially Paternal Origin of De Novo 11p13 Chromosome Deletions Revealed in Patients with Congenital Aniridia and WAGR Syndrome

The frequency of pathogenic large chromosome rearrangements detected in patients with different Mendelian diseases is truly diverse and can be remarkably high. Chromosome breaks could arise through different known mechanisms. Congenital PAX6-associated aniridia is a hereditary eye disorder caused by mutations or chromosome rearrangements involving the PAX6 gene. In our recent study, we identified 11p13 chromosome deletions in 30 out of 91 probands with congenital aniridia or WAGR syndrome (characterized by Wilms&rsquo; tumor, Aniridia, and Genitourinary abnormalities as well as mental Retardation). The loss of heterozygosity analysis (LOH) was performed in 10 families with de novo chromosome deletion in proband. In 7 out of 8 informative families, the analysis revealed that deletions occurred at the paternal allele. If paternal origin is not random, chromosome breaks could arise either (i) during spermiogenesis, which is possible due to specific male chromatin epigenetic program and its vulnerability to the breakage-causing factors, or (ii) in early zygotes at a time when chromosomes transmitted from different parents still carry epigenetic marks of the origin, which is also possible due to diverse and asymmetric epigenetic reprogramming occurring in male and female pronuclei. Some new data is needed to make a well-considered conclusion on the reasons for preferential paternal origin of 11p13 deletions

Relative Frequencies of PAX6 Mutational Events in a Russian Cohort of Aniridia Patients in Comparison with the World&rsquo;s Population and the Human Genome

Genome-wide sequencing metadata allows researchers to infer bias in the relative frequencies of mutational events and to predict putative mutagenic models. In addition, much less data could be useful in the evaluation of the mutational frequency spectrum and the prevalent local mutagenic process. Here we analyzed the PAX6 gene locus for mutational spectra obtained in our own and previous studies and compared them with data on other genes as well as the whole human genome. MLPA and Sanger sequencing were used for mutation searching in a cohort of 199 index patients from Russia with aniridia and aniridia-related phenotypes. The relative frequencies of different categories of PAX6 mutations were consistent with those previously reported by other researchers. The ratio between substitutions, small indels, and chromosome deletions in the 11p13 locus was within the interval previously published for 20 disease associated genomic loci, but corresponded to a higher end due to very high frequencies of small indels and chromosome deletions. The ratio between substitutions, small indels, and chromosome deletions for disease associated genes, including the PAX6 gene as well as the share of PAX6 missense mutations, differed considerably from those typical for the whole genome

Influence of Electrode Material and Electrolyze Conditions on the Electrochemical Oxidation of Thiocyanates

Исследовано электрохимическое окисление тиоцианатов на PbO2- и Pt-электродах в области высоких анодных потенциалов. Показано, что эффективность окисления тиоцианат-иона зависит от условий электролиза (рН раствора, концентрации субстрата) и материала электрода. Предполагается участие активных форм кислорода в процессе электроокисления SCN− , наряду с его прямым окислением на аноде.The electrochemical oxidation of thicyanates on PbO2 and Pt electrodes under the high potential region has been investigated. It has been showed that the oxidation efficiency of thiocyanate-ion depends on electrolyze conditions ( pH of solution, the reagent concentration) and the electrode material. There is proposed the participation of active oxygen forms in the SCN− electrolytic oxidation besides his direct oxidation on the anode

Electrochemical Oxidation of Thiocyanates by Active Oxygen Intermediates on Lead Dioxide Electrode

Исследовано электрохимическое окисление тиоцианатов на PbO2-электроде в области потенциалов образования активных форм кислорода. Показано, что эффективность окисления тиоцианат-иона зависит от потенциала электрода. Наряду с потенциалом на селективность процесса оказывает влияние способ проведения электролиза и соотношение α- и β-фаз PbO2 в активном слое электрода. Предполагается изменение механизма окисления тиоцианат-иона с увеличением потенциала анода.The electrochemical oxidation of thicyanates on PbO2 electrode in the potential region of forming of active oxygen forms has been investigated. The results show that oxidation efficiency of thiocyanate-ion depends on electrode potential. Besides the potential, the selectivity process influenced by the method of electrolyze and the ratios α- и β- PbO2 in active layer of electrode. The change of SCN−oxidation mechanism with increase of anode potential is supposed

Influence of Electrode Material and Electrolyze Conditions on the Electrochemical Oxidation of Thiocyanates

Исследовано электрохимическое окисление тиоцианатов на PbO2- и Pt-электродах в области высоких анодных потенциалов. Показано, что эффективность окисления тиоцианат-иона зависит от условий электролиза (рН раствора, концентрации субстрата) и материала электрода. Предполагается участие активных форм кислорода в процессе электроокисления SCN− , наряду с его прямым окислением на аноде.The electrochemical oxidation of thicyanates on PbO2 and Pt electrodes under the high potential region has been investigated. It has been showed that the oxidation efficiency of thiocyanate-ion depends on electrolyze conditions ( pH of solution, the reagent concentration) and the electrode material. There is proposed the participation of active oxygen forms in the SCN− electrolytic oxidation besides his direct oxidation on the anode

Electrochemical Oxidation of Thiocyanates by Active Oxygen Intermediates on Lead Dioxide Electrode

Исследовано электрохимическое окисление тиоцианатов на PbO2-электроде в области потенциалов образования активных форм кислорода. Показано, что эффективность окисления тиоцианат-иона зависит от потенциала электрода. Наряду с потенциалом на селективность процесса оказывает влияние способ проведения электролиза и соотношение α- и β-фаз PbO2 в активном слое электрода. Предполагается изменение механизма окисления тиоцианат-иона с увеличением потенциала анода.The electrochemical oxidation of thicyanates on PbO2 electrode in the potential region of forming of active oxygen forms has been investigated. The results show that oxidation efficiency of thiocyanate-ion depends on electrode potential. Besides the potential, the selectivity process influenced by the method of electrolyze and the ratios α- и β- PbO2 in active layer of electrode. The change of SCN−oxidation mechanism with increase of anode potential is supposed

Primary microcephaly case from the Karachay-Cherkess Republic poses an additional support for microcephaly and Seckel syndrome spectrum disorders

Abstract Background Primary microcephaly represents an example of clinically and genetically heterogeneous condition. Here we describe a case of primary microcephaly from the Karachay-Cherkess Republic, which was initially diagnosed with Seckel syndrome. Case presentation Clinical exome sequencing of the proband revealed a novel homozygous single nucleotide deletion in ASPM gene, c.1386delC, resulting in preterm termination codon. Population screening reveals allele frequency to be less than 0.005. Mutations in this gene were not previously associated with Seckel syndrome. Conclusions Our case represents an additional support for the clinical continuum between Seckel Syndrome and primary microcephaly