A pilot study to determine the relationship of changes in the characteristics of β1- and β2-adrenoreceptors against the background of the use of β2-agonists with clinically significant parameters in patients with cardiovascular pathology

Background: Comorbid cardiovascular and bronchoobstructive diseases worsens disease course and prognosis and causes difficulties in therapy. Effectiveness 2-agonists (cornerstone of bronchoobstructive pathology treatment) depends on -adrenoreceptors state. Therefore, a detailed study of the functional state of beta-adrenoreceptors is necessary. Aim: to evaluate the relationship of changes in the characteristics of 1- and 2-adrenoreceptors, against the background of the use of 2-agonists in patients with cardiovascular and bronchoobstructive diseases with clinically significant parameters. Methods: In the pilot single-center prospective study during 2.5 years 45 patients (15 with cardiovascular and 30 with bronchoobstructive diseases) were included. Anamnestic data and complaints were collected and laboratory and instrumental studies were performed. Modified radioligand analysis on blood T-lymphocytes using radiolabeled Cyanopindolol and unlabeled selective ligands (ICI 118551, CGP 20712) before and after salbutamol and formoterol was performed and the binding activity of 1- and 2-adrenoreceptors was determined. Results: The correlation analysis between clinically significant parameters and changes in the specific binding index of 1- and 2-adrenoreceptors confirmed its clinical relevance. In test with beta-agonists in cardiovascular and bronchoobstructive diseases patients, an increase in the specific binding index of 1-adrenoreceptors is associated with clinical, laboratory and instrumental parameters of a favorable course of the disease, and an increase in the specific binding index of 2-adrenoreceptors is associated with negative. In the cardiovascular group without bronchoobstructive diseases with salbutamol an increase in the specific binding index of 1-adrenoreceptors was associated with parameters of unfavorable disease course, while an increase in the specific binding index of 2-adrenoreceptors did not have a clear associative relationship with clinical characteristics. Conclusions: The association of changes in the specific binding index of 1- and 2-adrenoreceptors in patients with cardiovascular and bronchoobstructive diseases with clinically significant parameters during acute tests with short- and long-acting 2-agonists was revealed, which in the future may provide an opportunity to identify patients with an unfavorable course of the disease

Pharmacogenetics in Primary Headache Disorders

Primary headache disorders, such as migraine, tension-type headache (TTH), and cluster headache, belong to the most common neurological disorders affecting a high percentage of people worldwide. Headache induces a high burden for the affected individuals on the personal level, with a strong impact on life quality, daily life management, and causes immense costs for the healthcare systems. Although a relatively broad spectrum of different pharmacological classes for the treatment of headache disorders are available, treatment effectiveness is often limited by high variances in therapy responses. Genetic variants can influence the individual treatment success by influencing pharmacokinetics or pharmacodynamics of the therapeutic as investigated in the research field of pharmacogenetics. This review summarizes the current knowledge on important primary headache disorders, including migraine, TTH, and cluster headache. We also summarize current acute and preventive treatment options for the three headache disorders based on drug classes and compounds taking important therapy guidelines into consideration. Importantly, the work summarizes and discusses the role of genetic polymorphisms regarding their impact on metabolism safety and the effect of therapeutics that are used to treat migraine, cluster headache, and TTH exploring drug classes such as nonsteroidal anti-inflammatory drugs, triptans, antidepressants, anticonvulsants, calcium channel blockers, drugs with effect on the renin-angiotensin system, and novel headache therapeutics such as ditans, anti-calcitonin-gene-related peptide antibodies, and gepants. Genetic variants in important phase I-, II-, and III-associated genes such as cytochrome P450 genes, UGT genes, and different transporter genes are scrutinized as well as variants in genes important for pharmacodynamics and several functions outside the pharmacokinetic and pharmacodynamic spectrum. Finally, the article evaluates the potential and limitations of pharmacogenetic approaches for individual therapy adjustments in headache disorders

Tryptophan-Assisted Synthesis Reduces Bimetallic Gold/Silver Nanoparticle Cytotoxicity and Improves Biological Activity

Aiming to reduce the potential in vivo hepato-and neph‐ rotoxicity of Ag/Au bimetallic nanoparticles (NPs) stabi‐ lized by sodium dodecyl sulphate (SDS), an approach involving a simultaneous reduction of silver nitrate and tetrachlorauratic acid using tryptophan (Trp) as a reduc‐ ing/stabilizing agent was applied during NP synthesis. The obtained Ag/Au/Trp NPs (5-15 nm sized) were able to form stable aggregates with an average size of 370-450 nm and were potentially less toxic than Ag/Au/SDS in relation to a mouse model system based on clinical biochemical param‐ eters and oxidative damage product estimation. Ag/Au/Trp NPs were shown to exhibit anticancer activity in relation to a Lewis lung carcinoma model. The data generated from the present study support the fact that the use of tryptophan in NP synthesis is effective in attenuating the potential hepatotoxicity and nephrotoxicity of NPs during their in vivo application

Exploitation of knowledge databases in the synthesis of zinc(II) malonates with photo-sensitive and photo-insensitive N,N′-containing linkers

Photoinitiated solid-state reactions are known to affect the physical properties of coordination polymers, such as fluorescence and sorption behaviour, and also afford extraordinary architectures (e.g. three-periodic structures with polyorganic ligands). However, the construction of novel photo-sensitive coordination polymers requires an understanding of the factors which govern the mutual disposition of reactive fragments. A series of zinc(II) malonate complexes with 1,2-bis(pyridin-4-yl)ethylene and its photo-insensitive analogues has been synthesized for the purpose of systematic analysis of their underlying nets and mutual disposition of N-donor ligands. The application of a big data-set analysis for the prediction of a variety of possible complex compositions, coordination environments and networks for a four-component system has been demonstrated for the first time. Seven of the nine compounds possess one of the highly probable topologies for their underlying nets; in addition, two novel closely related four-coordinated networks were obtained. Complexes containing 1,2-bis(pyridin-4-yl)ethylene and 1,2-bis(pyridin-4-yl)ethane form isoreticular compounds more readily than those with 4,4′-bipyridine and 1,2-bis(pyridin-4-yl)ethylene. The effects of the precursor, either zinc(II) nitrate or zinc(II) acetate, on the composition and dimensionality of the resulting architecture are discussed. For three of the four novel complexes containing 1,2-bis(pyridin-4-yl)ethylene, the single-crystal-to-single-crystal [2 + 2] cycloaddition reactions were carried out. UV irradiation of these crystals afforded either the 0D→1D or the 3D→3D transformations, with and without network changes. One of the two 3D→3D transformations was accompanied by solvent (H2O) cleavage

Migration from the Newly Independent States. 25 Years After the Collapse of the USSR

This book discusses international migration in the newly independent states after the collapse of the Soviet Union, which involved millions of people. Written by authors from 15 countries, it summarizes the population movement over the post-Soviet territories, both within the newly independent states and in other countries over the past 25 years. It focuses on the volume of migration flows, the number and socio-demographic characteristics of migrants, migration factors and the situation of migrants in receiving countries. The authors, who include demographers, economists, geographers, anthropologists, sociologists and political scientists, used various methods and sources of information, such as censuses, administrative statistics, the results of mass sample surveys and in-depth interviews. This heterogeneity highlights the multifaceted nature of the topic of migration movements