Вплив емульсії евгенолу в полісорбаті-80 на клінічні штами грибів Сandida albicans

В переліку збудників кандидозних уражень вуха Candida albicans займає домінуючу позицію. Пріоритетною і актуальною залишається розробка нових протигрибкових засобів, альтернативним джерелом яких можуть бути ефірні олії рослин та їх компоненти. Одним із таких засобів з антисептичною, протизапальною і знеболюючою дією є речовина класу фенолів – евгенол. Тому, метою даного дослідження було вивчення ефективності протитгрибкової дії євгенолу, емульгованого в полісорбаті-80 на клінічні штами C. albicans, виділені від хворих на зовнішній отомікоз. Дослідження було проведено на 6 клінічних штамах C. albicans, виділених із слухового проходу хворих на зовнішній отит. Діагноз грибкового захворювання встановлювали на підставі результатів клініко-лабораторного, мікроскопічного та мікологічного досліджень патологічного матеріалу. Аналіз мікологічного дослідження показав, що переважно висівались представники роду Aspergillus та Penicillium і лише у 7% гриби роду Candida. Домінуючим видом, який мав клінічне значення, залишався C. albicans. Результати наших досліджень показали високий рівень протигрибкової активності евгенолу на всі клінічні штами C. albicans, у тому числі виражену як інгібуючу, так і фунгіцидну дію. В постмікостатичних концентраціях евгенол викликав часткове пригнічення розмноження досліджуваних клінічних штамів грибів, яке змінювалось наступним підвищенням інтенсивності темпів самовідтворення. В результаті проведених досліджень було встановлено, що C. аlbicans є домінуючим видом серед грибів роду Candida в структурі мікробного профілю отомікозів. Евгенол, емульгований в полісорбати-80, проявляє високу протигрибкову дію на клінічні штами Сandida аlbicans. В постмікостатичних концентраціях евгенол викликає часткове пригнічення розмноження досліджуваних клінічних штамів грибів, яке змінювалось наступним підвищенням інтенсивності темпів самовідтворення.Candida albicans occupies a dominant position in the list of causative agents of candidal lesions of the ear. The development of new antifungal agents, an alternative source of which can be herbal essential oils and their components, remains a priority. One such agent with antiseptic, anti-inflammatory, and analgesic action is eugenol which is a phenol substance. Therefore, this article was aimed to study the effectiveness of the antifungal action of eugenol emulsified in Polysorbate-80 against clinical strains of C. albicans isolated from patients with external otomycosis. The study was performed using 6 clinical strains of C. albicans isolated from the ear canal of patients with otitis externa. The diagnosis of fungal disease was established based on the results of clinical and laboratory (microscopical and mycological) studies of pathological material. Analysis of mycological research showed that mainly representatives of the genus Aspergillus and Penicillium were revealed and only in 7% there were Candida genus fungi. C. albicans remained the dominant species of clinical significance. The results of our studies showed a high level of antifungal activity of eugenol on all clinical strains of C. albicans, including a remarkable inhibitory and fungicidal effect. At postmycostatic concentrations, the eugenol caused partial inhibition of reproduction of the clinical strains of fungi, which was replaced by a subsequent increased cell reproduction rate. So, the investigation has shown that C. albicans is the dominant species among fungi of the Candida genus in the structure of the microbial profile of otomycoses. The eugenol, emulsified in Polysorbate-80, has a high antifungal effect against clinical strains of C. albicans. At postmycostatic concentrations, the eugenol caused partial inhibition of reproduction of the clinical strains of fungi, which was replaced by a subsequent increase cell reproduction rate

Predicting opioid therapy safety in pancreatic cancer patients

Background - Obligatory use of strong opioids for treating chronic pain syndrome in patients with pancreatic cancer provides the implementation of opioid-associated adverse reactions. Genetic and non-genetic risk factors are predictive of the opioid therapy safety. Contemporary methods of information analysis allow using prognostic risk models for practical application. Objective - Identification of significant risk factors for the development of opioid-associated adverse drug reactions in patients with chronic pain syndrome against the background of pancreatic cancer. Material and Methods - The study included 90 patients with chronic pain against the background of pancreatic cancer, randomized at a ratio of 1: 1. Group 1 received morphine sulfate (MS), group 2 received fentanyl transdermal therapeutic system (FTTS) with standard adjuvant therapy (ketoprofen, diazepam, amitriptyline). To assess pain level, the 10-point Digital Rating Scale, the Visual Analogue Scale and the pain questionnaires were used. The assessment of the treatment safety was conducted by the Naranjo Scale. Assessment of prognostic genetic and non-genetic factors was carried out using ROC analysis with calculation of AUC (the area under the ROC-curve). Results - Prognostic models of good quality were determined with the optimal ratio of sensitivity and specificity for the influence of genetic and non-genetic risk factors on the development of opioid-associated adverse drug reactions (OA-ADRs) in comparison groups. Various prognostic factors, complementing each other, were identified in the comparison groups. Conclusion - The following OA-ADRs predicting factors were identified: for FTTS-associated nausea and vomiting - age and carriage of rs7438135 AG genotype of UGT2B7 gene; for local reactions - the sum of points on the ESAS scale and carriage of rs7438135 AA genotype of UGT2B7 gene; for difficulty urinating - the level of glomerular filtration rate; for neurotoxicity - the level of AST and bilirubin, and the carriage of rs1128503 GG genotype of ABCB1 gene; for pruritus - carriage of rs1045642642 AA genotype of ABCB1 gene. The prognostic factors for the implementation of MS-associated neurotoxicity were age and comorbidity; for dry mouth was predicted best from the sum of points on the MMCE scale; weakness was predicted by the carriage of rs7668258 TT genotype of UGT2B7 gene. © 2020, LLC Science and Innovations

Pharmacoeconomic analysis of the application of strong opioids for the treatment of chronic pain syndrome in patients with pancreatic cancer [Фармакоэкономический анализ применения сильных опиоидов для лечения хронического болевого синдрома у пациентов с раком поджелудочной железы]

Objective: to evaluate the clinical and economic feasibility of opioid therapy based on the analysis of its cost and effectiveness in patients with chronic pain syndrome in pancreatic cancer. Material and methods. An observational prospective study in parallel groups of patients with chronic pain syndrome associated with pancreatic cancer was carried out. The analysis of cost minimization and cost-effectiveness was applied, as well as pharmacoeconomic modeling, which included the construction of a decision tree in patients receiving morphine sulfate (n=45) and fentanyl TTS (n=45) for pain relief. The sensitivity of the obtained data was assessed using one-way analysis. Results. It was shown that the treatment of chronic pain syndrome in patients with pancreatic cancer with opioid analgesics as part of combined treatment is the least expensive in the morphine sulfate group (incremental cost-effectiveness ratio 144.93). Based on the results of modeling, the prognostic factors of influence on the cost of analgesic therapy were determined: the cost of combined analgesic therapy, the cost of treatment of adverse reactions, and the cost-effectiveness ratio. Conclusion. Analgesic therapy of chronic pain syndrome with morphine sulfate in patients with pancreatic cancer is pharmacoeconomically feasible. © 2021 IRBIS LLC. All Rights Reserved

Tearing Instability in a Force-free Collisionless Pair Plasma

We investigate sissipation process of magnetic field energy in collisionless electron-positron (pair) plasmas by using two-dimensional, fully relativistic, electromagnetic particle-in-cell code. We consider the force-free magnetic configuration with no current-driven Bunneman instability. A half of initial magnetic field energy dissipates by the tearing instability. The dissipated energy can be converted into plasma kinetic energy as well as plasma heating. The trowth rate of tearing instability is two times larger than the heory of elefcron-ion tearing instabilty

Pharmacokinetic and pharmacogenetic aspects of personalized analgetic therapy with fentanil tts in clinical oncology

The aim of the study was the pharmacokinetic and pharmacogenetic analysis of analgetic efficacy and safety of transdermal fentanyl for cancer patients. Material and methods. A comprehensive search for journal articles published between 2012 and 2017 was carried out using PubMed, Scopus, Web of Science, and E-library databases. Results. The analysis of the data showed that pharmacokinetic and pharmacogenetic factors can influence the interindividual variability of analgesic therapy with fentanyl TTC for cancer patients, predetermining phenotypic differences in the efficacy and safety of analgesia. Enforced polypharmacotherapy with the use of inducers or inhibitors of the CYP3A4 isoenzyme activity can significantly change the effectiveness of analgesic therapy and result in undesirable side effects of strong opioids. Contradictory data on the effect of some single nucleotide polymorphisms of metabolic genes, transport genes and mu-opioid receptor genes dictate the necessity of further studies in this field. Conclusion. To date, there is no single explanation for interindividual variability of analgesic therapy with fentanyl TTS. A comprehensive assessment of the pharmacokinetic and pharmacogenetic factors affecting the efficacy and safety of analgesic therapy with potent opioids is a tool of a personalized approach for anesthesia in clinical oncology. © 2018 Tomsk National Research Medical Center of the Russian Academy of Sciences. All rights reserved

Фармакокинетические и фармакогенетические аспекты персонализированной анальгетической терапии фентанилом ТТС в онкологии

The aim of the study was the pharmacokinetic and pharmacogenetic analysis of analgetic efficacy and safety of transdermal fentanyl for cancer patients. Material and methods. A comprehensive search for journal articles published between 2012 and 2017 was carried out using PubMed, Scopus, Web of Science, and E-library databases. Results. The analysis of the data showed that pharmacokinetic and pharmacogenetic factors can influence the interindividual variability of analgesic therapy with fentanyl TTC for cancer patients, predetermining phenotypic differences in the efficacy and safety of analgesia. Enforced polypharmacotherapy with the use of inducers or inhibitors of the CYP3A4 isoenzyme activity can significantly change the effectiveness of analgesic therapy and result in undesirable side effects of strong opioids. Contradictory data on the effect of some single nucleotide polymorphisms of metabolic genes, transport genes and mu-opioid receptor genes dictate the necessity of further studies in this field. Conclusion. To date, there is no single explanation for interindividual variability of analgesic therapy with fentanyl TTS. A comprehensive assessment of the pharmacokinetic and pharmacogenetic factors affecting the efficacy and safety of analgesic therapy with potent opioids is a tool of a personalized approach for anesthesia in clinical oncology. © 2018 Tomsk National Research Medical Center of the Russian Academy of Sciences. All rights reserved.Цель исследования - анализ отечественной и зарубежной литературы о влиянии фармакокинетических и фармакогенетических факторов на эффективность и безопасность анальгетической терапии трансдермальным фентанилом в онкологии. Материал и методы. Проведен поиск русско- и англоязычных статей в научных базах PubMed, Scopus, Web of Science, E-library по ключевым словам: фентанил ТТС, фармакокинетика, фармакогенетика, хронический болевой синдром, онкология, персонализация, обзор литературы, fentanyl TTS, pharmacokinetics, pharmacogenetics, chronic pain syndrome, oncology, personalization, literature review. Включались публикации с 2012 по 2017 г. Результаты. Анализ данных показал возможность влияния фармакокинетических и фармакогенетических факторов на межиндивидуальную изменчивость анальгетической терапии фентанилом ТТС в онкологии, предопределяя фенотипические различия по эффективности и безопасности обезболивания. Вынужденная полифармакотерапия с применением индукторов или ингибиторов активности изофермента CYP3A4 может значимо изменять эффективность и обеспечивать реализацию нежелательных побочных реакций сильных опиоидов. Противоречивые данные о влиянии носительства некоторых одиночных нуклеотидных полиморфизмов генов метаболизма, генов-транспортеров и генов μ-опиоидных рецепторов диктуют проведение дальнейших исследований в этой области. Заключение. На сегодняшний день отсутствует единое объяснение межиндивидуальной изменчивости анальгетической терапии фентанилом ТТС. Комплексная оценка фармакокинетических и фармакогенетических факторов, влияющих на эффективность и безопасность анальгетической терапии сильными опиоидами, является инструментом персонализированного подхода при проведении обезболивания в клинической онкологии

Chronic pain syndrome in patients with pancreatic cancer: individual therapy and its pathogenetic background

This review presents the results of recent studies on the role of pathogenic mechanisms of chronic pain syndrome in patients with pancreatic cancer. The authors searched Russian and international databases, including MedLine, PubMed, NEL elibrary.ru, Wiley Online Library, Web of Science, Oxford University Press, SAGE Premier, for the period from 1996 to 2016 (10 years). Our results demonstrate the preconditions for multimodal analgesic therapy in anesthesia and pain treatment. We show the key role of selecting basic pharmacological groups of drugs for the patients with pancreatic cancer with chronic pain syndrome. The dependence of patient survival on the intensity, diversity and complexity of pancreatic pain in pancreatic cancer means that individual therapy is extremely important as inadequate pain relief can have profound negative effects on the psychosocial and physical well-being of pancreatic cancer patients and their relatives

Эффективность и безопасность опиоидной терапии хронического болевого синдрома у пациентов с раком поджелудочной железы: клинико-патогенетические особенности

Aim. To study the influence of clinical and pathogenetic factors in patients with pancreatic cancer on the efficacy and safety of analgesic therapy of chronic pain syndrome. Materials and methods. Clinical features of formation of chronic pain syndrome predetermining the efficacy and safety of analgesic therapy were studied in 82 patients with pancreatic cancer. Results. The efficacy and safety of opioids in the comparison groups of morphine sulfate, fentanyl TTC and oxycodone / naloxone in patients with pancreatic cancer was shown.Цель. Изучить влияние клинико - патогенетических факторов у пациентов с раком поджелудочной железы на эффективность и безопасность анальгетической терапии хронического болевого синдрома. Материалы и методы. У 82 пациентов с раком поджелудочной железы изучены клинические особенности формирования хронического болевого синдрома, предопределяющие эффективность и безопасность анальгетической терапии. Результаты. Показана эффективность и безопасность опиоидов в группах сравнения морфина сульфата, фентанила ТТС и оксикодона / налоксона у пациентов с раком поджелудочной железы