АКТУАЛЬНЫЕ ВОПРОСЫ ДИАГНОСТИКИ И ЛЕЧЕНИЯ КАРЦИНОИДНОЙ БОЛЕЗНИ СЕРДЦА (КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ)

ABSTRACT. We report a case of progressive carcinoid heart disease (cHD) having caused readmission of a patient after excision of endocardium with arterial intima and multiple valve replacement. The data prove that in cases of combined valve heart disease of the right side it is necessary to assume the high probability of the carcinoid disease. Therefore, in spite of the high value of echocardiography, multispiral computed tomography (MScT), confirming the diagnosis, detecting metastases in different organs and determining the localization of the primary tumor, becomes particularly important. open heart surgery can be effective only when accompanied by operative therapy for the primary tumor with the use of somatostatin analogues. РЕЗЮМЕ. Представлены данные, свидетельствующие о прогрессировании карциноидной болезни сердца, послужившие поводом для повторной госпитализации больной после эндокардинтимэктомии и множественного протезирования клапанов. Данные подтверждают, что в случаях сочетанного поражения клапанов правых отделов сердца следует исходить из высокой вероятности их карциноидного поражения. В этой связи, наряду с эхокардиографией особую ценность приобретает мультиспиральная компьютерная томография, позволяющая подтвердить диагноз, выявить метастазы в различных органах и определить локализацию первичного очага. Операция на открытом сердце может быть эффективной только в сочетании с хирургическим лечением первичной опухоли и использованием аналогов соматостатина

Local and average fields inside surface-disordered waveguides: Resonances in the one-dimensional Anderson localization regime

We investigate the one-dimensional propagation of waves in the Anderson localization regime, for a single-mode, surface disordered waveguide. We make use of both an analytical formulation and rigorous numerical simulation calculations. The occurrence of anomalously large transmission coefficients for given realizations and/or frequencies is studied, revealing huge field intensity concentration inside the disordered waveguide. The analytically predicted s-like dependence of the average intensity, being in good agreement with the numerical results for moderately long systems, fails to explain the intensity distribution observed deep in the localized regime. The average contribution to the field intensity from the resonances that are above a threshold transmission coefficient $T_{c}$ is a broad distribution with a large maximum at/near mid-waveguide, depending universally (for given $T_{c}$) on the ratio of the length of the disorder segment to the localization length, $L/\xi$. The same universality is observed in the spatial distribution of the intensity inside typical (non-resonant with respect to the transmission coefficient) realizations, presenting a s-like shape similar to that of the total average intensity for $T_{c}$ close to 1, which decays faster the lower is $T_{c}$. Evidence is given of the self-averaging nature of the random quantity $\log[I(x)]/x\simeq -1/\xi$. Higher-order moments of the intensity are also shown.Comment: 9 pages, 9 figure

Utilization of an In Vivo Reporter for High Throughput Identification of Branched Small Molecule Regulators of Hypoxic Adaptation

SummarySmall molecules inhibiting hypoxia inducible factor (HIF) prolyl hydroxylases (PHDs) are the focus of drug development efforts directed toward the treatment of ischemia and metabolic imbalance. A cell-based reporter produced by fusing HIF-1α oxygen degradable domain (ODD) to luciferase was shown to work as a capture assay monitoring stability of the overexpressed luciferase-labeled HIF PHD substrate under conditions more physiological than in vitro test tubes. High throughput screening identified novel catechol and oxyquinoline pharmacophores with a “branching motif” immediately adjacent to a Fe-binding motif that fits selectively into the HIF PHD active site in in silico models. In accord with their structure-activity relationship in the primary screen, the best “hits” stabilize HIF1α, upregulate known HIF target genes in a human neuronal line, and exert neuroprotective effects in established model of oxidative stress in cortical neurons

Guidelines for consideration of bats in lighting projects.

Eighty percent of the world’s population are currently exposed to light-polluted skies, and the Milky Way is no longer visible to more than a third of humanity. The pace the light pollution is increasing is faster than global population growth and economic development. While environmental conditions at night are being dramatically and rapidly altered, circadian rhythms, behaviour and ecology of plants and animals are imminently influenced. In the same time, effects of artificial lighting, various illumination schemes and spectra on biodiversity, including bats, are currently insufficiently understood, whereas only a vague notion of required mitigation and compensation activities exists among decision-makers and other parties involved in lighting projects. Although the bats are almost exclusively nocturnal and extremely sensitive to multiple effects of light pollution, its negative impact on bats alongside essential measures needed to preserve unfragmented nightscapes for these animals are often disregarded during impact assessments, planning and operation. In this volume, we tried to compile available evidence related to the effect of artificial light at night on the European bats. Based on the current state of knowledge, solutions are proposed concerning possible ways to avoid, mitigate and compensate the adverse effects which lighting projects may have on bats and their functional habitats. We also outlined research priorities for future studies, required for in-depth understanding of the problem and assessing efficiency of proposed mitigative measures

Development of Neh2-Luciferase Reporter and Its Application for High Throughput Screening and Real-Time Monitoring of Nrf2 Activators

SummaryThe NF-E2-related factor 2 (Nrf2) is a key transcriptional regulator of antioxidant defense and detoxification. To directly monitor stabilization of Nrf2, we fused its Neh2 domain, responsible for the interaction with its nucleocytoplasmic regulator, Keap1, to firefly luciferase (Neh2-luciferase). We show that Neh2 domain is sufficient for recognition, ubiquitination, and proteasomal degradation of Neh2-luciferase fusion protein. The Neh2-luc reporter system allows direct monitoring of the adaptive response to redox stress and classification of drugs based on the time course of reporter activation. The reporter was used to screen the Spectrum library of 2000 biologically active compounds to identify activators of Nrf2. The most robust and yet nontoxic Nrf2 activators found—nordihydroguaiaretic acid, fisetin, and gedunin—induced astrocyte-dependent neuroprotection from oxidative stress via an Nrf2-dependent mechanism

ПРОГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ ХРОНИЧЕСКОЙ БОЛЕЗНИ ПОЧЕК У БОЛЬНЫХ С ОСТРЫМ КОРОНАРНЫМ СИНДРОМОМ

The study of acute coronary syndrome (ACS) in patients with chronic kidney disease (CKD) is one of the areas of modern cardiology. The prevalence, course, prognosis and tactics of treatment of myocardial infarction in CKD are not well understood. The analysis of literature sources allows us to state that CKD in ACS doubles the risk of immediate and long-term death and adverse cardiovascular events. It is necessary to determine the CKD stage to predict the hospital and long-term mortality of the infarct patient. It is difficult to diagnose ACS at advanced stages of CKD. CKD should be considered an independent risk of death after percutaneous coronary intervention and coronary bypass surgery.Изучение острого коронарного синдрома (ОКС) у больных хронической болезнью почек (ХБП) является одним из направлений современной кардиологии. Распространенность, течение, прогноз и тактика лечения инфаркта миокарда при ХБП недостаточно изучены. Анализ литературных источников позволяет констатировать: ХБП при ОКС удваивает риск смерти (РС) и неблагоприятных сердечно-сосудистых событий в ближайшем и отдаленном периодах; определение стадии ХБП необходимо с целью прогнозирования госпитальной и отдаленной смертности инфарктных больных; диагностика ОКС на поздних стадиях ХБП сложна; ХБП следует считать независимым РС после проведения чрескожных коронарных вмешательств и коронарного шунтирования

БЛИЖАЙШИЕ И ОТДАЛЕННЫЕ РЕЗУЛЬТАТЫ РАЗЛИЧНЫХ СТРАТЕГИЙ ЛЕЧЕНИЯ БОЛЬНЫХ С КРУПНООЧАГОВЫМ ПОВТОРНЫМ ИНФАРКТОМ МИОКАРДА

Aim of study: to assess the effectiveness of invasive treatment strategies in patients with repeated myocardial infarction (rMI). We compared results of three treatment strategies in 453 patients with rMI admitted to the Institute from 2003 to 2011 and analyzed long-term results (up to 2016): 139 roentgen-endovascular coronary interventions (RECI) (various types), including the delayed procedures (performed 24–72 h later), 25 surgical myocardial revascularizations 8–12 weeks after the onset of rMI and 289 cases of conservative therapy. Cardiovascular mortality had been assessed in 138 patients with different treatment strategies for 5 years after the discharge.Findings show that rMI is a predictor of high risk of death associated with high in-hospital and longterm mortality in the absence of reperfusion therapy. RECI in the early stages of rMI does not exclude its later performance. Different types of interventions, including the delayed ones, significantly reduce the incidence of complications and deaths, which occurence remains high in the absence of interventions. however, in a significant portion of patients with rMI, the severity of coronary lesions limits the possibility of RECI performance, determining indications for elective surgical myocardial revascularization. Coronary artery bypass surgery performed after myocardial scarring prevents the growth of left ventricular dysfunction, improves its contractile function, and prolongs the life of patients. Reperfusion strategies such as various types of RECI and/or delayed surgical myocardial revascularization improve the effectiveness of treatment in patients with rMI.Цель исследования: оценка эффективности инвазивных стратегий лечения больных с повторным инфарктом миокарда (пИМ). Проведено сопоставление результатов трех стратегий лечения 453 больных с пИМ, госпитализированных в институт с 2003 по 2011 г. с анализом отдаленных результатов до 2016 г.: различных видов рентгенэндоваскулярных коронарных вмешательств (РКВ), включая отсроченные, выполненные через 24–72 ч (n=139) от начала ИМ; хирургической реваскуляризации миокарда через 8–12 нед от начала пИМ (n=25) и консервативной терапии (n=289). В течение 5 лет после выписки у 138 больных с различными стратегиями лечения оцени- вали общую летальность, в том числе от сердечно-сосудистых заболеваний.Полученные данные свидетельствуют о том, что пИМ является предиктором высокого риска смерти, связанного с отсутствием реперфузионной терапии с высокой госпитальной и отдаленной летальностью. Установлено, что РКВ в ранние сроки пИМ не исключает возможности более позднего их применения. Отсроченные вмешательства существенно сокращают частоту осложнений и смертельных исходов. Вместе с тем, у значительной части больных с пИМ тяжесть поражения коронарного русла ограничивает возможности применения РКВ, определяя показания к хирургической реваскуляризации миокарда. Шунтирование коронарных артерий, выполненное после рубцевания миокарда, предотвращает нарастание дисфункции левого желудочка, улучшает его сократительную функцию и увеличивает продолжительность жизни больных. Применение реперфузионных стратегий в виде различных видов РКВ, в том числе отсроченных и/или хирургической реваскуляризации миокарда позволяет повысить эффективность лечения больных с пИМ

К МЕТОДИКЕ ОЦЕНКИ ПЕРФУЗИИ МИОКАРДА ЛЕВОГО ЖЕЛУДОЧКА ПРИ ИНФАРКТЕ МИОКАРДА С ПОМОЩЬЮ ОДНОФОТОННОЙ ЭМИССИОННОЙ КОМПЬЮТЕРНОЙ ТОМОГРАФИИ

SUMMARY. On the basis of single photon emission computed tomography of the myocardium (SPECT) with Technetril 99mTc performed in 81 patients with myocardial infarction (MI), we confirmed the proportion of myocardial segments of the left ventricle (LV) with varying degrees of RP inclusion and, therefore, with varying degrees of perfusion impairment. In 75% of patients, reduction of hypoperfusion area in the remote period after myocardial infarction has been revealed compared to the acute period. The relation between slow ECG evolution with the severe impairment of left ventricular myocardial perfusion has been showed. The relation between the degree of impairment of LV myocardial perfusion (by SPECT) and its contraction (according to the two-dimensional echocardiogram) has been revealed. It is shown that one of the leading factors in the restoration of myocardial perfusion is the time of intracoronary intervention. РЕЗЮМЕ. На основании проведения у 81 больного инфарктом миокарда (ИМ) перфузионной однофотонной эмиссионной компьютерной томографии (ОФЭКТ) миокарда с 99mTc-технетрилом уточнено соотношение сегментов миокарда левого желудочка (ЛЖ) с разной степенью включения радиофармпрепарата и, следовательно, с разной степенью нарушения перфузии. У 75% пациентов установлено сокращение площади гипоперфузии в отдаленный период инфаркта по сравнению с острым. Продемонстрирована связь замедленной ЭКГ-эволюции ИМ с глубокими расстройствами перфузии миокарда ЛЖ. Выявлена взаимосвязь степени нарушения перфузии миокарда ЛЖ (по данным ОФЭКТ) и его сократимости (по данным двухмерной Эхо-КГ). Показано, что одним из ведущих факторов восстановления перфузии миокарда является время выполнения внутрико- ронарного вмешательства.