Effectiveness of Allopurinol and Quercetin inclusion in a complex treatment of stable angina pectoris – peculiarities of biomarkers and homeostatic indices changes

Objective – to study the effectiveness of Allopurinol and Quercetin inclusion in a complex treatment of stable angina pectoris and peculiarities of biomarkers and homeostatic indices changes. Materials and Methods. 120 patients with the diagnosis of stable angina pectoris (SAP) and hyperuricemia (HU) were examined and three groups were formed: patients receiving a complex standard therapy (70 persons – 58,33%), patients receiving the standard therapy with addition of Allopurinol (23 persons – 19,17%), and patients receiving Quercetin in addition to the standard therapy (27 individuals – 22,50%). At the beginning of in-patient treatment and 6 months later during out-patient period all patients were clinically and laboratory examined (uric acid, total cholesterol (TC), triglycerides (TG), creatinine, NT-proBNP, С-reactive protein (СRP) and total testosterone (TT) in the blood serum). Results. Reduced content of TC and TG in the 1st, 2nd and 3rd groups of a complex treatment was found (р<0,05; р<0,001 and р<0,001 respectively) with prevailing effect of Allopurinol compared with the standard treatment. In case of standard treatment elevated initial plasma levels of uric acid and creatinine were found (р<0,001 in both cases) that can probable be explained by the loop diuretics administration to achieve euvolemic condition. The indicated effect of diuretics is compensated by Allopurinol and Quercetin inclusion in the therapy (р<0,001 by all indices) with prevailing effect of Allopurinol compared with the standard (р<0,05). In comparison with the standard therapy addition of both Allopurinol and Quercetin promotes reduction of NT-proBNP initial content (in both cases р<0,05). A positive dynamics concerning inflammatory activity with reduction of the initial concentration of CRP (р<0,001) is achieved only with addition of Allopurinol to the therapy. Conclusions. Addition of Allopurinol into the standard therapy of patients with SAP and asymptomatic HU promotes the dynamics of inflammatory activity with reduction of CRP initial concentration. Addition of Allopurinol or Quercetin to the standard therapy normalizes dyslipidemia by means of TC and TG content decreasing, improves renal function and reduces creatinine level with prevailing effect of Allopurinol, promotes reduction of NT-proBNP initial content. Inflammatory activity and dyslipidemia with elevated levels of TC and TG are the criteria for additional Allopurinol administration for the patients with SAP and asymptomatic HU

Statins interfere with the attachment of S. cerevisiae mtDNA to the inner mitochondrial membrane

The 3-hydroxy-3-methylglutaryl-CoA reductase, a key enzyme of the mevalonate pathway for the synthesis of cholesterol in mammals (ergosterol in fungi), is inhibited by statins, a class of cholesterol lowering drugs. Indeed, statins are in a wide medical use, yet statins treatment could induce side effects as hepatotoxicity and myopathy in patients. We used Saccharomyces cerevisiae as a model to investigate the effects of statins on mitochondria. We demonstrate that statins are active in S.cerevisiae by lowering the ergosterol content in cells and interfering with the attachment of mitochondrial DNA to the inner mitochondrial membrane. Experiments on murine myoblasts confirmed these results in mammals. We propose that the instability of mitochondrial DNA is an early indirect target of statins

LARP7 family proteins have conserved function in telomerase assembly

Understanding the intricacies of telomerase regulation is crucial due to the potential health benefits of modifying its activity. Telomerase is composed of an RNA component and reverse transcriptase. However, additional factors required during biogenesis vary between species. Here we have identified fission yeast Lar7 as a member of the conserved LARP7 family, which includes the Tetrahymena telomerase-binding protein p65 and human LARP7. We show that Lar7 has conserved RNA-recognition motifs, which bind telomerase RNA to protect it from exosomal degradation. In addition, Lar7 is required to stabilise the association of telomerase RNA with the protective complex LSm2-8, and telomerase reverse transcriptase. Lar7 remains a component of the mature telomerase complex and is required for telomerase localisation to the telomere. Collectively, we demonstrate that Lar7 is a crucial player in fission yeast telomerase biogenesis, similarly to p65 in Tetrahymena, and highlight the LARP7 family as a conserved factor in telomere maintenance

Whole exome sequencing links dental tumor to an autosomal-dominant mutation in ANO5 gene associated with gnathodiaphyseal dysplasia and muscle dystrophies

Tumors of the jaws may represent different human disorders and frequently associate with pathologic bone fractures. In this report, we analyzed two affected siblings from a family of Russian origin, with a history of dental tumors of the jaws, in correspondence to original clinical diagnosis of cementoma consistent with gigantiform cementoma (GC, OMIM: 137575). Whole exome sequencing revealed the heterozygous missense mutation c.1067G \u3e A (p.Cys356Tyr) in ANO5 gene in these patients. To date, autosomal-dominant mutations have been described in the ANO5 gene for gnathodiaphyseal dysplasia (GDD, OMIM: 166260), and multiple recessive mutations have been described in the gene for muscle dystrophies (OMIM: 613319, 611307); the same amino acid (Cys) at the position 356 is mutated in GDD. These genetic data and similar clinical phenotypes demonstrate that the GC and GDD likely represent the same type of bone pathology. Our data illustrate the significance of mutations in single amino-acid position for particular bone tissue pathology. Modifying role of genetic variations in another gene on the severity of the monogenic trait pathology is also suggested. Finally, we propose the model explaining the tissue-specific manifestation of clinically distant bone and muscle diseases linked to mutations in one gene

LARP7 family proteins have conserved function in telomerase assembly

Understanding the intricacies of telomerase regulation is crucial due to the potential health benefits of modifying its activity. Telomerase is composed of an RNA component and reverse transcriptase. However, additional factors required during biogenesis vary between species. Here we have identified fission yeast Lar7 as a member of the conserved LARP7 family, which includes the Tetrahymena telomerase-binding protein p65 and human LARP7. We show that Lar7 has conserved RNA-recognition motifs, which bind telomerase RNA to protect it from exosomal degradation. In addition, Lar7 is required to stabilise the association of telomerase RNA with the protective complex LSm2–8, and telomerase reverse transcriptase. Lar7 remains a component of the mature telomerase complex and is required for telomerase localisation to the telomere. Collectively, we demonstrate that Lar7 is a crucial player in fission yeast telomerase biogenesis, similarly to p65 in Tetrahymena, and highlight the LARP7 family as a conserved factor in telomere maintenance

State work and the testing concours of citizenship

Anyone trying to be a citizen has to pass through a set of practices trying to be a state. This paper investigates some of the ways testing practices calibrate citizens, and in doing so, perform “the state.” The paper focuses on three forms of citizenship testing, which it considers exemplary forms of “state work,” and which all, in various ways, concern “migration.” First, the constitution of a “border crossing,” which requires an identity test configured by deceptibility. Second, the Dutch asylum process, in which “being gay” can, in certain cases, be reason for being granted asylum, but where “being gay” is also the outcome of an examination organized by suspicion. And third, the Dutch measurement of immigrants’ “integration,” which is comprised of a testing process in which such factishes as “being a member of society” and “being modern” surface. Citizenship is analyzed in this paper as accrued and (re)configured along a migration trajectory that takes shape as a testing concours, meaning that subjects become citizens along a trajectory of testing practices. In contributing both to work on states and citizenship, and to work on testing, this paper thus puts forward the concept of citizenship testing as state work, where “state work is the term for that kind of labor that most knows itself as comparison, equivalency, and exchange in the social realm” (Harney, 2002, pp. 10–11). Throughout the testing practices discussed here, comparison, equivalency, and exchange figure prominently as the practical achievements of crafting states and citizens

Actual aspects of organic agricultural development in Ukraine

The monograph presents a conceptual analysis of the development of all sectors of organic production in Ukraine, the problems of sustainable increase in the efficiency of agrobiocenoses, the economic aspects of the formation of organic production according to European standards, and the analysis of opportunities for the agrarian sector. The approaches to the application of new methods and tools in organic production are described. The monograph is prezented for specialists, employments of the agrarian sector, scientists, professors, students and masters, all those who are interested in the specified range of questions that are being analyzed

Towards framing the global in Global Development: prospects for development geography

This paper examines data in the public sphere on the global scope of geography’s UKRI Global Challenges Research Fund (GCRF) projects. Building on decolonial critiques of development research, I argue that geography should frame ‘the global’ of global research as a sphere of ethical choices in research design and practice. The distribution of funded projects in the UKRI Gateway data suggests geographers succeed where they extend on the more worthy aspects of the discipline’s Area Studies legacy. The discipline’s engagements with Early Career Researchers, international colleagues, and the development sector, however, have potentially been reshaped by GCRF and thus need closer examination. While the UK government has brought the GCRF programme to a close, further work on these themes should inform the next iteration of global research. The ethical choices which make research global will remain fundamental to equitable design and impact in Global Development projects, thus scholars in development geography should prepare to make their projects more transparent and accountable

Characteristics of mukoviscisidosis in the southern regions of Russia

Introduction. Cystic fibrosis (CF) is a  hereditary disease with genetic heterogeneity and clinical polymorphism. Expanding the range of knowledge about the characteristics of the course of the disease in different regions is important to achieve the goal of improving the quality and life expectancy.Purpose. Comparative analysis of the features of the course of CF in the subjects of the Southern Federal District, Stavropol Territory.Methods. Data from the National Register of Patients of the RF MV 2016 were used. Results: there are clinical and genetic features between the regions of the Southern Federal District and the Stavropol Territory of the North Caucasus Federal District and in general with the Russian Federation. Analysis of the data showed differences in indicators: the proportion of patients aged ≥ 18 is the lowest in the Republic of Crimea (14.9%), in the Rostov region the lowest average age of patients (9.0 ± 6.3), and the lowest age of diagnosis 2.2 ± 3.1 years. Late terms of diagnosis were revealed in the Stavropol Territory (4.0 ± 8.0 years), but here there is one of the highest average age of CF patients (14.1 ± 11.5), the proportion of adult patients (23.3%) and the lowest allelic frequency of F508del, which is determined by the high number of patients with a “soft” genotype. There is a high proportion of patients with an undetermined genotype. A low proportion of two identified genetic variants of the CFTR gene is registered in patients of the Republic of Crimea. A low frequency of Burkholderia cepacia complex and Achromobacter spp was revealed, and a high infection with non-tuberculous mycobacteria was revealed in the Rostov region. FEV1 in children and adults was lower in Rostov Region and Stavropol Territory. In all regions, there is a discrepancy between the seeding of flora and azithromycin therapy and the severity of the genotype with the use of pancreatic enzymes.Conclusions. Analysis of the data of the registry, which allows substantiating the need to study the regional characteristics of the course of CF in order to differentiate the planning of measures to improve the quality of medical care for patients with CF