A new era in treatment of cardiac amyloidosis: an overview of the Congress of cardiology

2021 ◽  
Author(s):  
И.Е. Стрелкова
Keyword(s):  
Cardiac Amyloidosis ◽  
Amyloid Fibrils ◽  
Decisive Role ◽  
Fibrillar Structure ◽  
New Era ◽  
Vital Functions ◽  
Age Related ◽  
Other Substances ◽  
Amyloid Cardiomyopathy

Амилоидоз – это группа заболеваний, характеризующихся накоплением в интерстиции различных органов и тканей белка специфической фибриллярной структуры. Понятие «амилоидоз» объединяет более 30 различных по своей патофизиологии состояний, в основе каждого из которых лежит нарушение синтеза 30 различных белков-предшественников. Однако 95% амилоидных кардиомиопатий связаны всего с двумя белками: белком, образованным из легких цепей иммуноглобулинов, и белком транстиретином. Определение белка-предшественника является краеугольным камнем ведения пациента с амилоидной кардиомиопатией. Транстиретин – это белок-переносчик тироксина, ретинола и других веществ, выполняющий жизненно важные функции. По наследственным или возрастным причинам происходит нарушение синтеза транстиретина в печени, и образующиеся мономеры, попадая в кровь, образуют токсичные промежуточные продукты и амилоидные фибриллы. Амилоидоз сердца (или амилоидная кардиомиопатия) до недавнего времени считался редким заболеванием. В недалеком прошлом возможности терапии амилоидоза сердца ограничивались назначением диуретиков, антагонистов минералокортикоидных рецепторов и антикоагулянтов, так как другие средства не переносятся пациентами или переносятся в минимальных дозах. С появлением в России первого средства специфического лечения транстиретиновой амилоидной кардиомиопатии резко возросла необходимость в повышении настороженности в отношении транстиретинового амилоидоза среди врачей-терапевтов и кардиологов и во внедрении современных алгоритмов диагностики данного заболевания. Своевременное выявление транстиретинового амилоидоза и грамотная дифференциальная диагностика от других видов амилоидной кардиомиопатии могут сыграть решающую роль в прогнозе заболевания. Препарат тафамидис доказанно снижает частоту госпитализаций и летальность у пациентов с транстиретиновым амилоидозом. Amyloidosis is a group of diseases characterized by accumulation of a protein of a specific fibrillar structure in the interstitium of various organs and tissues. The concept of ≪amyloidosis≫ unites more than 30 different pathophysiological conditions, each of which is based on abnormal synthesis of 30 different precursor proteins. However, 95% of amyloid cardiomyopathies are associated with just two proteins: a protein derived from light chains of immunoglobulins and a protein called transthyretin. Determination of the precursor protein is a cornerstone of management of patients with amyloid cardiomyopathy. Transthyretin is a carrier protein of thyroxine, retinol and other substances, that performs vital functions. For hereditary or age-related reasons, TTR misfolding occurs in the liver. The resulting monomers, entering blood, form toxic intermediate products and amyloid fibrils. Cardiac amyloidosis (or amyloid cardiomyopathy) used to be considered a rare disease. In the recent past, possibilities of therapy for cardiac amyloidosis were limited by prescription of diuretics, mineralocorticoid receptor antagonists and anticoagulants, since other drugs are not tolerated well by patients or are tolerated in minimal doses. Advent of the first drug specific for treatment of transthyretin amyloid cardiomyopathy in Russia increased a need of awareness of ATTR-CM among general practitioners and cardiologists, and introduction of modern diagnostic algorithms for this disease. Timely detection and competent differential diagnosis of ATTR-CM from other types of amyloid cardiomyopathy can play a decisive role in the prognosis of this disease. Tafamidis is a treatment that was shown to reduce mortality and CV-related hospitalization in ATTR-CM patients.

THE SUBJECT FIELD OF INSTITUTIONAL EDUCATION: THE SENSE AND PROSPECTS OF DEVELOPMENT IN UKRAINE

2020 ◽  
pp. 25-38
Author(s):  
Irina Mordous
Keyword(s):  
Decisive Role ◽  
Subject Field ◽  
National Education ◽  
Progressive Development ◽  
Separate Area ◽  
Economic Transformations ◽  
The Difference ◽  
The Individual ◽  
Political Economic

The development of modern civilization attests to its decisive role in the progressive development of institutions. They identified the difference between Western civilization and the rest of the world. Confirmation of the institutional advantages of the West was its early industrialization. The genesis and formation of institutionalism in its ideological and conceptualmethodological orientation occurs as a process alternative to neoclassic in the context of world heterodoxia, which quickly spread in social science. Highlighting institutional education as a separate area of sociocultural activity is determined by the factor of differentiation of institutional theory as a whole. A feature of institutional education is its orientation toward the individual and his/her transformation into a personality. The content of institutional education is revealed through the analysis of the institution, which includes a set of established customs, traditions, ways of thinking, behavioral stereotypes of individuals and social groups. The dynamics of socio-political, economic transformations in Ukraine requires a review of the foundations of national education and determination of the prospects for its development in the 21st century in the context of institutionalism.

Flame ionization detector response to coeluting hydrocarbons and carbon disulphide and its application to the determination of the sum of C6-C11 alkanes and cycloalkanes in air

1983 ◽  
Vol 48 (3) ◽  
pp. 722-734
Author(s):  
Martin Koval
Keyword(s):  
Carbon Disulphide ◽  
Internal Standard ◽  
Calibration Procedure ◽  
Detector Response ◽  
Column Temperature ◽  
Flame Ionization ◽  
Other Substances ◽  
Flame Ionisation Detector ◽  
Ionisation Detector

The flame ionisation detector response to C6-C11 aliphatic hydrocarbon solutions in carbon disulphide in the concentration range between 1.3-9.5 mg ml-1 retained lineary despite the excess of solvent entering the detector simultaneously with the analyte. Pure carbon disulphide exhibited a small positive detector response which did not interfere in calibration procedure and which, under certain GC conditions, inverted to negative values. This response was not proportional to the injected volume and was strongly influenced by the column temperature and/or bleed. On the basis of these findings, a method compatible with the widely used charcoal tube carbon disulphide desorption procedure was developed and evaluated. It consists of static desorption of the sum of aliphatic alkanes and cycloalkanes from the activated charcoal after which an internal standard is added to the supernatant eluate. The resulting carbon disulphide solution is analysed on a highly polar stationary phase 1,2,3-tris(2-cyanoethoxy)propane where the solvent and the analyte coelute in a single peak, the height of which is practically proportional to the sum of alkanes and cycloalkanes present. This also makes determinations of other substances present in the sample more simple. The field test of the proposed method yielded values comparable in precision and accuracy with a control infrared spectrophotometric method.

Transthyretin Amyloid Cardiomyopathy—Current and Future Therapies

2021 ◽  
pp. 106002802110003
Author(s):  
Jankhna D. Yadav ◽  
Harjot Othee ◽  
Kelly A. Chan ◽  
Damen C. Man ◽  
Paul P. Belliveau ◽  
...  
Keyword(s):  
Cardiac Amyloidosis ◽  
Complex Disease ◽  
Clinical Presentation ◽  
Target Therapy ◽  
Data Extraction ◽  
Organ Transplant ◽  
Standard Of Care ◽  
Transthyretin Amyloidosis ◽  
Treatment Benefits ◽  
Amyloid Cardiomyopathy

Objective: To describe the clinical presentation of transthyretin amyloid cardiomyopathy (ATTR-CM) and discuss current treatments and investigational products and their effect on patient outcomes. Data Sources: A literature search was performed in PubMed (September 2018 to December 2020) using the following keywords: transthyretin amyloidosis, cardiomyopathy, polyneuropathy and transthyretin amyloid cardiomyopathy, monoclonal light-chain, tafamidis, cardiac amyloidosis, ATTR cardiomyopathy, green tea and inhibition of cardiac amyloidosis, AG10, tolcapone, tolcapone and leptomeningeal ATTR, PRX004, NI006, patisiran, inotersen, vutrisiran, AKCEA-TTR-LRx, and NTLA-2001. Study Selection and Data Extraction: Clinical trials were evaluated for evidence supporting pharmacology, safety, efficacy, and measured outcomes. Data Synthesis: Until 2019, there were no approved treatments for ATTR-CM. Treatment consisted of symptom management and organ transplant. Nonpharmacological and pharmacological treatments focused on the symptoms of heart failure (HF) associated with ATTR-CM. However, there are several emerging therapies recently approved or in development to address the underlying pathophysiology. Treatment classes for ATTR-CM include transthyretin stabilizers, human monoclonal antibodies, gene silencers, and CRISPR/Cas9 gene editing. Relevance to Patient Care and Clinical Practice: ATTR-CM is a complex disease in which amyloidosis causes cardiomyopathy. Underdiagnosis is attributed to the clinical presentation being heterogeneous, indistinguishable from HF caused by other etiologies, and the need for invasive testing modalities, including endomyocardial biopsy. Improved diagnostic approaches along with targeted therapies can slow disease progression and enhance patient quality of life. Conclusion: Diagnostic modalities along with biomarker and genetic testing could detect disease earlier and target therapy more accurately. Novel therapies demonstrate potential treatment benefits and can help shape the standard of care for these patients.

Crucial Effects of Weightlessness on Human Orientation

1993 ◽  
Vol 3 (3) ◽  
pp. 307-314 ◽  
Author(s):  
H. Mittelstaedt ◽  
S. Glasauer
Keyword(s):  
Visual Cues ◽  
Decisive Role ◽  
Experimental Conditions ◽  
Subjective Vertical ◽  
Independent Components ◽  
Human Orientation ◽  
The Mean ◽  
Trunk Tilt

This contribution examines the consequences of two remarkable experiences of subjects in weightlessness, 1) the missing of sensations of trunk tilt and of the respective concomitant reflexes when the head is tilted with respect to the trunk, and 2) the persistence of a perception of “up” and “down,” that is, of the polarity of the subjective vertical (SV) in the absence of, as well as in contradiction to, visual cues. The first disproves that the necessary head-to-trunk coordinate transformation be achieved by adding representations of the respective angles gained by utricles and neck receptors, but corroborates an extant model of cross-multiplication of utricular, saccular, and neck receptor components. The second indicates the existence of force-independent components in the determination of the SV. Although the number of subjects is still small and experimental conditions are not as homogeneous as desired, measurements and/or reports on the ground, in parabolic, and in space flight point to the decisive role of the saccular z-bias, that is, of a difference of the mean resting discharges of saccular units polarized in the rostrad and the caudad (±z-) direction.

scholarly journals Age-Related Immunoreactivity Profiles to Diverse Mycobacterial Antigens in BCG-Vaccinated Chinese Population

2021 ◽  
Vol 11 ◽  
Author(s):  
Qing-yuan Yang ◽  
Yu-tong Zhang ◽  
Jia-ni Xiao ◽  
Yu-shuo Liang ◽  
Ping Ji ◽  
...  
Keyword(s):  
Elispot Assay ◽  
Vaccine Development ◽  
Age Related ◽  
Healthy Donors ◽  
Latent Tb ◽  
Latent Tb Infection ◽  
Mycobacterial Antigens ◽  
Selection Of

Long-term immunoreactivity to mycobacterial antigens in Bovis Calmette-Guérin (BCG)-vaccinated population is not well investigated. Herein, 361 volunteer healthy donors (HDs) with neonatal BCG vaccination from Shanghai region (China) were enrolled. They were subdivided into ESAT-6/CFP10- (E6C10-) and ESAT-6/CFP10+ (E6C10+) groups based on gamma-interferon release assays (IGRAs). Three mycobacterial antigens, including Rv0934, Rv3006, and Rv3841, were subjected to the determination of immunoreactivity by ELISPOT assay. The immunoreactivities to three mycobacterial antigens were firstly compared among TB patients (N=39), E6C10+ HDs (N=78, 21.61% of HDs) and E6C10- HDs (N=283, 78.39% of HDs). It was revealed that Rv3006 was dominant upon M.tb infection, while Rv3841 was likely to be more responsive upon latent TB infection. In E6C10- population, the immunoreactivity to Rv3841 maintained along with aging, whereas those to Rv3006 and Rv0934 attenuated in E6C10- HDs older than 45 years old. Our study implies the shift of dominant antigens at different infection statuses, providing the clues for the selection of mycobacterial antigens in vaccine development and precision revaccination in the future.

scholarly journals Cardiac Amyloidosis: A Review of Current Imaging Techniques

2021 ◽  
Vol 8 ◽  
Author(s):  
Yousuf Razvi ◽  
Rishi K. Patel ◽  
Marianna Fontana ◽  
Julian D. Gillmore
Keyword(s):  
Bone Scintigraphy ◽  
Cardiac Amyloidosis ◽  
Tissue Characterization ◽  
Amyloid Fibrils ◽  
Imaging Techniques ◽  
Significant Proportion ◽  
Disease Process ◽  
Heterogenous Group ◽  
Pathological Disease ◽  
Over Time

Systemic amyloidosis is a rare, heterogenous group of diseases characterized by extracellular infiltration and deposition of amyloid fibrils. Cardiac amyloidosis (CA) occurs when these fibrils deposit within the myocardium. Untreated, this inevitably leads to progressive heart failure and fatality. Historically, treatment has remained supportive, however, there are now targeted disease-modifying therapeutics available to patients with CA. Advances in echocardiography, cardiac magnetic resonance (CMR) and repurposed bone scintigraphy have led to a surge in diagnoses of CA and diagnosis at an earlier stage of the disease natural history. CMR has inherent advantages in tissue characterization which has allowed us to better understand the pathological disease process behind CA. Combined with specialist assessment and repurposed bone scintigraphy, diagnosis of CA can be made without the need for invasive histology in a significant proportion of patients. With existing targeted therapeutics, and novel agents being developed, understanding these imaging modalities is crucial to achieving early diagnosis for patients with CA. This will allow for early treatment intervention, accurate monitoring of disease course over time, and thereby improve the length and quality of life of patients with a disease that historically had an extremely poor prognosis. In this review, we discuss key radiological features of CA, focusing on the two most common types; immunoglobulin light chain (AL) and transthyretin (ATTR) CA. We highlight recent advances in imaging techniques particularly in respect of their clinical application and utility in diagnosis of CA as well as for tracking disease change over time.

scholarly journals On-Surface Mechanochemistry Synthesis of Non-Alternant Non-Benzenoid Aromatic Compounds Containing 4 to 8-Membered Rings

2020 ◽  
Author(s):  
Benjamin Mallada ◽  
Bruno de la Torre ◽  
Jesus I. Mendieta-Moreno ◽  
Dana Nachtigalova ◽  
Adam Matej ◽  
...  
Keyword(s):  
Organic Chemistry ◽  
Polycyclic Aromatic Hydrocarbons ◽  
Aromatic Hydrocarbons ◽  
Decisive Role ◽  
Closed Shell ◽  
Considerable Effort ◽  
Aromatic Character ◽  
Polycyclic Aromatic ◽  
Traditional Approaches

Synthesis of polycyclic aromatic hydrocarbons containing various non-benzenoid rings remains a big challenge facing contemporary organic chemistry despite a considerable effort made over the last decades. Herein, we present a novel route, employing on-surface mechanochemistry, to synthesize non-alternant polycyclic aromatic hydrocarbon containing up to four distinct kinds of non-benzenoid rings. We show that the surface-induced mechanical constrains imposed on strained helical reactants play a decisive role leading to the formation of products, energetically unfavorable in solution, with a peculiar ring current stabilizing the aromatic character of the π-conjugated system. Determination of the chemical and electronic structures of the most frequent product reveals its closed-shell character and low band gap. The present study renders a new route for the synthesis of novel non-alternant polycyclic aromatic hydrocarbons or other hydrocarbons not available by traditional approaches of organic chemistry in solution.

scholarly journals Polymorphisms of pleiotropic genes ABCC11 and ACE in Abkhazians and the longevity phenomenon

2019 ◽  
pp. 29-36
Author(s):  
С.В. Макаров ◽  
М.К. Карапетян ◽  
К.Б. Квеквескири ◽  
В.А. Спицын
Keyword(s):  
Multiple Drug Resistance ◽  
Control Group ◽  
Multiple Drug ◽  
Ace Gene ◽  
Caucasus Region ◽  
Gene Insertion ◽  
Vital Functions ◽  
Genotype Frequencies ◽  
Age Related ◽  
And Control

Изучение наследственных факторов в детерминации долголетия представляется весьма актуальным в связи с ростом средней продолжительности жизни, поиском возможностей продления «здорового» периода в позднем отногенезе. Феномен высокой продолжительности жизни всегда вызывал особый интерес исследователей, а его изучение представляется наиболее перспективным в популяциях с достаточно большой долей долгожителей. С давних времен известны случаи ярко выраженного активного долголетия в регионе Кавказа. У долгожителей Абхазии темпы соматического развития, уровень обменных процессов и меньшая интенсивность возрастной инволюции скелета указывали на относительно «здоровый» тип старения. Среди генетических факторов, которые потенциально могли бы играть важную роль в достижении долголетия, особенно перспективным представляется изучение плейотропных генов, действие которых проявляется во множественных эффектах и обладающих высокой функциональной значимостью. Среди них особый интерес представляют те, которые определяют эффективность функционирования сердечно-сосудистой системы, а также особенности, влияющие на темп созревания и старения организма. К числу таких генов можно отнести ген ангиотензин-превращающего фермента (ACE) и ген множественной лекарственной устойчивости (ABCC11). Целью исследования был поиск закономерностей в характере распределения полиморфных вариантов плеойтропных генов ABCC11 и ACE в популяции абхазов в связи с возрастом обследуемых и наличием долгожителей в выборке. В качестве материала исследования были собраны образцы клеток буккального эпителия от коренных жителей Абхазии, подразделенных на две группы: старшего возраста (75-101 год, 79 человек) и контрольную ( 97 индивидов в возрасте от 16 до 33 лет ). Анализ распределений частот генотипов и аллелей полиморфизма 538G>A (rs17822931) гена ABCC11 показал, что группы старшего возраста и контроля очень сходны между собой и достоверные различия между выборками отсутствуют. Генотипирование по инсерционно-делеционному полиморфизму гена ACE (rs1799752) осуществлялось методом ПЦР-ПДАФ. Для контрольной группы абхазов установлены следующие частоты генотипов: II = 0,186; ID = 0,412; DD = 0,402, частоты аллелей I и D оказались равны 0,392 и 0,608 соответственно. Группа старшего возраста по частотам генотипов существенно не отличалась от контроля, генотипы II/ID/DD были распределены в соотношении 0,088/0,380/0,532, а частоты аллелей I и D оказались равны 0,278 и 0,722 соответственно. В результате исследования выявлено, что частота аллеля делеции по инсерционно-делеционному полиморфизму в гене ACE в старшей возрастной группе абхазов достоверно повышена по сравнению с контрольной группой. The study of the phenomenon of longevity is the most promising in populations with a fairly large proportion of centenarians. Since old times cases of pronounced active longevity have been widely known in the Caucasus region. The complexity of age-related processes of aging assumes the involvement of multiple complex factors that have affect on life expectancy. Therefore the study of the pleiotropic genes with their multiple effects and functions could be helpful in that case. The angiotensin I-converting enzyme (ACE) gene and the multiple drug resistance gene ( ABCC11) are of great interest because of their high importance for essential vital functions. The aim of the study was the search for correlations in the frequencies distribution of polymorphic variants of pleoitropic genes ABCC11 and ACE in the population of Abkhazians with the longevity. The material included the DNA samples from indigenous residents of Abkhazia. They were divided into two groups: older age (N = 79) and control (N = 97). The differences in the frequencies distribution of 538G>A genotypes and alleles of the gene ABCC11 in the older group and control were not significant. ACE gene insertion-deletion polymorphism ( rs1799752) genotyping was performed by PCR-AFLP. The genotype frequencies were : II = 0.186; ID = 0.412; DD = 0.402, allele frequencies I and D were equal to 0.392 and 0.608 for the control group of Abkhazians. The older group did not differ significantly from the control in genotype frequencies, the ratio for II/ID/DD genotypes were as 0.088/0.380/0.532, and the frequencies of alleles I and D corresponded to 0.278 and 0.722. The obtained results revealed that the ACE gene deletion allele frequency was significantly increased in the older group of Abkhazians.

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