Neoglycolipids Micelle-like Structures as a Basis for Drug Delivery Systems

Targeted drug delivery is one of the most promising tasks of nanomedicine, as this is a real way to increase the effectiveness of therapeutic effects against many diseases. In this regard, the development of new inexpensive highly effective stimulating and non-immunogenic drug delivery systems (DDS) is of great importance. In this work new molecular candidates were proposed and studied for the creation of such systems based on the use of new compounds, neoglycolipids. It is shown that these compounds are capable of self-association in aqueous solutions and can serve as potential carriers of drug compounds with targeted delivery determined by their terminal groups (in particular, glycans). The processes of their associates formation and features of their structure are investigated. The results show that these selforganizing nanoscale systems can be used as a basis for developing new drug delivery systems. Keywords: neoglycolipids, micelle-like structures, small-angle X-ray scattering, molecular dynamics simulatio

Features of the ancestral bilaterian inferred from Platynereis dumerilii ParaHox genes

Background The ParaHox gene cluster is the evolutionary sister to the Hox cluster. Whilst the role of the Hox cluster in patterning the anterior-posterior axis of bilaterian animals is well established, and the organisation of vertebrate Hox clusters is intimately linked to gene regulation, much less is known about the more recently discovered ParaHox cluster. ParaHox gene clustering, and its relationship to expression, has only been described in deuterostomes. Conventional protostome models (Drosophila melanogaster and Caenorhabditis elegans) are secondarily derived with respect to ParaHox genes, suffering gene loss and cluster break-up. Results We provide the first evidence for ParaHox gene clustering from a less-derived protostome animal, the annelid Platynereis dumerilii. Clustering of these genes is thus not a sole preserve of the deuterostome lineage within Bilateria. This protostome ParaHox cluster is not entirely intact however, with Pdu-Cdx being on the opposite end of the same chromosome arm from Pdu-Gsx and Pdu-Xlox. From the genomic sequence around the P. dumerilii ParaHox genes the neighbouring genes are identified, compared with other taxa, and the ancestral arrangement deduced. Conclusion We relate the organisation of the ParaHox genes to their expression, and from comparisons with other taxa hypothesise that a relatively complex pattern of ParaHox gene expression existed in the protostome-deuterostome ancestor, which was secondarily simplified along several invertebrate lineages. Detailed comparisons of the gene content around the ParaHox genes enables the reconstruction of the genome surrounding the ParaHox cluster of the protostome-deuterostome ancestor, which existed over 550 million years ago.Publisher PDFPeer reviewe

Nasolacrimal Duct Obstruction Secondary to Radioactive Iodine-131 Therapy for Differentiated Thyroid Cancer

Deterministic effects of medical exposure to ionising radiation can be associated with both the effectiveness of treatment and adverse drug reactions to it. The latter may drastically deteriorate the quality of life of a patient after radionuclide therapy. In addition, the regulations of the Russian Federation require indicating the effective dose of radiation as a measure of damage (risk), but the presence of a deterministic effect in individual organs and tissues complicates monitoring and recording patient exposure doses. The aim of the study was to investigate the effect of radiopharmaceuticals containing 131I on the development of secondary nasolacrimal duct obstruction (NLDO). Materials and methods: the study of secondary NLDO predictors analysed medical history data, post-therapy head-and-neck scintigrams, and methods to prepare patients for treatment. It involved sodium iodide, 131I, formulated as a solution (marketing authorisation number: FS-002065) by the FSUE Federal Center of Nuclear Medicine Projects Design and Development of the FMBA of Russia. Results: the authors unambiguously localised the lacrimal ducts in post-therapy 131I scintigrams of the head and neck and quantified 131I uptake ratios for the lacrimal duct area. Also, they identified a set of NLDO predictors: the age of a patient, the administered activity, the administration of recombinant human thyroid-stimulating hormone, the 131I uptake ratio, etc. The article describes a method for identifying the groups at risk of NLDO following radioiodine therapy for differentiated thyroid cancer. Conclusions: secondary NLDO is a deterministic effect of 131I exposure. The authors have developed a new method for predicting secondary NLDO by a combination of the patient’s individual parameters and treatment plan; the identified predictors help to personalise radioiodine therapy. The authors suggest the following: to include information on secondary NLDO as a complication of therapy to the SmPC section on undesirable effects; to develop approaches to secondary NLDO prevention; and to improve the algorithms for reporting adverse events in case of delayed manifestation and those for following patients up in the medical organisations having administered the radiopharmaceutical or in other medical organisations being applied to for medical care afterwards

Drug-Induced Atrial Fibrillation / Atrial Flutter

Drug-induced atrial fibrillation / flutter (DIAF) is a serious and potentially life-threatening complication of pharmacotherapy. Purpose of the work: systematization and analysis of scientific literature data on drugs, the use of which can cause the development of DIAF, as well as on epidemiology, pathophysiological mechanisms, risk factors, clinical picture, diagnosis and differential diagnosis, treatment and prevention of DIAF. Analysis of the literature has shown that many groups of drugs can cause the development of DIAF, with a greater frequency while taking anticancer drugs, drugs for the treatment of the cardiovascular, bronchopulmonary and central nervous systems. The mechanisms and main risk factors for the development of DIAF have not been finally established and are known only for certain drugs, therefore, this section requires further study. The main symptoms of DIAF are due to the severity of tachycardia and their influence on the parameters of central hemodynamics. For diagnosis, it is necessary to conduct an electrocardiogram (ECG) and Holter monitoring of an ECG and echocardiography. Differential diagnosis should be made with AF, which may be caused by other causes, as well as other rhythm and conduction disturbances. Successful treatment of DIAF is based on the principle of rapid recognition and immediate discontinuation of drugs (if possible), the use of which potentially caused the development of adverse drug reactions (ADR). The choice of management strategy: heart rate control or rhythm control, as well as the method of achievement (medication or non-medication), depends on the specific clinical situation. For the prevention of DIAF, it is necessary to instruct patients about possible symptoms and recommend self-monitoring of the pulse. It is important for practitioners to be wary of the risk of DIAF due to the variety of drugs that can potentially cause this ADR

Вторичная облитерация слезоотводящих путей при проведении радиойодтерапии 131I дифференцированного рака щитовидной железы

Deterministic effects of medical exposure to ionising radiation can be associated with both the effectiveness of treatment and adverse drug reactions to it. The latter may drastically deteriorate the quality of life of a patient after radionuclide therapy. In addition, the regulations of the Russian Federation require indicating the effective dose of radiation as a measure of damage (risk), but the presence of a deterministic effect in individual organs and tissues complicates monitoring and recording patient exposure doses. The aim of the study was to investigate the effect of radiopharmaceuticals containing 131I on the development of secondary nasolacrimal duct obstruction (NLDO). Materials and methods: the study of secondary NLDO predictors analysed medical history data, post-therapy head-and-neck scintigrams, and methods to prepare patients for treatment. It involved sodium iodide, 131I, formulated as a solution (marketing authorisation number: FS-002065) by the FSUE Federal Center of Nuclear Medicine Projects Design and Development of the FMBA of Russia. Results: the authors unambiguously localised the lacrimal ducts in post-therapy 131I scintigrams of the head and neck and quantified 131I uptake ratios for the lacrimal duct area. Also, they identified a set of NLDO predictors: the age of a patient, the administered activity, the administration of recombinant human thyroid-stimulating hormone, the 131I uptake ratio, etc. The article describes a method for identifying the groups at risk of NLDO following radioiodine therapy for differentiated thyroid cancer. Conclusions: secondary NLDO is a deterministic effect of 131I exposure. The authors have developed a new method for predicting secondary NLDO by a combination of the patient’s individual parameters and treatment plan; the identified predictors help to personalise radioiodine therapy. The authors suggest the following: to include information on secondary NLDO as a complication of therapy to the SmPC section on undesirable effects; to develop approaches to secondary NLDO prevention; and to improve the algorithms for reporting adverse events in case of delayed manifestation and those for following patients up in the medical organisations having administered the radiopharmaceutical or in other medical organisations being applied to for medical care afterwards.Детерминированные эффекты воздействия ионизирующего излучения в ядерной медицине могут быть ассоциированы как с эффективностью терапевтического воздействия, так и с нежелательными реакциями, которые могут резко ухудшить качество жизни пациента после проведения радионуклидной терапии. Согласно требованиям нормативно-правовых актов Российской Федерации необходимо указать эффективную дозу облучения в качестве меры ущерба (риска), однако контроль и учет доз облучения пациента затруднен при наличии детерминированного воздействия излучения в отдельных органах и тканях. Цель работы: изучение влияния радиофармацевтических лекарственных препаратов с содержанием 131I на развитие облитерации слезоотводящих путей. Материалы и методы: при исследовании предикторов возникновения вторичной облитерации были рассмотрены данные из анамнеза пациентов, посттерапевтические сцинтиграфические изображения головы и шеи, проанализирован способ подготовки пациентов к лечению. Лекарственное средство — Натрия йодид, 131I, субстанция-раствор, ФС-002065, производства ФГУП «Федеральный центр по проектированию и развитию объектов ядерной медицины» ФМБА России. Результаты: достоверно определена локализация слезоотводящих путей на посттерапевтических сцинтиграфических изображениях головы и шеи с 131I; количественно определены индексы накопления 131I в области слезоотводящих путей. Выявлен комплекс предикторов облитерации слезоотводящих путей: возраст пациента, введенная активность, введение рекомбинантного аналога тиреотропного гормона гипофиза человека, индекс накопления 131I и другие. Описана методика определения группы риска возникновения облитерации слезоотводящих путей после радиойодтерапии по поводу дифференцированного рака щитовидной железы. Выводы: вторичная облитерация слезоотводящих путей — детерминированный эффект воздействия 131I. Выявленные предикторы позволяют персонализировать проведение радиойодтерапии. Разработан новый способ прогноза развития вторичной облитерации слезоотводящих путей на основе комплекса персональных параметров пациентов и индивидуального плана лечения. Предлагается включить информацию об осложнениях в виде вторичной облитерации слезоотводящих путей в раздел «Побочное действие» инструкции по медицинскому применению лекарственного препарата, разработать подходы к профилактике развития вторичной облитерации слезоотводящих путей, усовершенствовать алгоритмы подачи информации о неблагоприятных событиях в случае отсроченного проявления заболеваний и алгоритмы динамического наблюдения за пациентом непосредственно в медицинских учреждениях, где был применен лекарственный препарат, а также в других учреждениях, в которые пациент обращается за оказанием медицинской помощи

COVID-19 and Thyroid Disease: Clinical Course and Prognosis

The aim is to analyze current scientific data on the prevalence of thyroid dysfunction in patients with COVID-19 and to evaluate the relationship between possible complications of COVID-19 and vaccination. Materials and methods. Open digital archive of journal articles on biomedical and biological sciences of the National Institutes of Health (USA), developed by the National Center for Biotechnological Information of the National Medical Library (USA) – PubMed, Google Academy and Academic Journals. Results. The development of thyroid diseases in SARS-CoV-2 may be associated with various mechanisms of its damage, including an excessive immune response, infection-induced immunodeficiency, or direct cell damage due to significant tissue tropism and high affinity of SARS-CoV-2 to thyroid tissue. Possible mechanisms of formation of post-vaccination dysfunction of the thyroid gland are proposed. Conclusions. Thyroid hormone deficiency is associated with an increased risk of adverse events and in-hospital mortality of COVID-19 and depended on the age of the patient. The severe course of Covid-19 is characterized by an increase in the prevalence of TT secondary to destructive or inflammatory thyroiditis. Thyroid-related thyrotoxicosis exacerbates the clinical course of comorbidities and long-term consequences, such as autoimmune hypothyroidism, which occurs in patients of all ages and with any severity of COVID-19. The prevalence of TD in patients with COVID-19 varies from 13 to 64 %. 2. The presence of thyroid dysfunction is positively correlated with the clinical severity of COVID-19. Patients with confirmed thyroid disease should receive COVID-19 vaccine to reduce the risk of morbidity and mortality from COVID-19 infectio