Thermal phase transitions in rotating QCD with dynamical quarks

Relativistic rotation causes a change of QCD critical temperatures. Various phenomenological and effective models predict a decrease of the critical temperatures in rotating QCD. Nevertheless, lattice simulations showed that the critical temperature in gluodynamics increases due to rotation. We extend the lattice study to the theory with dynamical fermions. We present the first lattice results for rotating QCD with $N_f=2$ dynamical clover-improved Wilson quarks. We also study separately the effect of rotation on gluonic and fermionic degrees of freedom. It is shown that separate rotations of gluons and fermions have opposite effects on the critical temperatures. In aggregate, the pseudo-critical temperatures in QCD increase with angular velocity. Dependence of the results on the pion mass is also discussed.Comment: 10 pages, 5 figures, Proceedings of the 39th International Symposium on Lattice Field Theory, 8th-13th August, 2022, Bonn, German

Genetic Risk Factors for Adverse Drug Reactions

The use of medicines may in some cases be associated with the development of drug-induced diseases (DIDs) аnd other adverse drug reactions (ADRs), which leads to an increase in morbidity/mortality rates, and/or symptoms forcing a patient to seek medical attention or resulting in hospitalisation. ADRs may develop due to changes in a patient’s genotype, which entail an inadequate pharmacological response. The aim of the study was to analyse and summarise literature data on genetic risk factors that cause DIDs аnd other ADRs. It was shown that the polymorphism of genes encoding enzymes of drug metabolism (CYP, UGT, NAT, TPMT, EPHX, GST, etc.) or carriers (transporters) of drugs (P-gp, BCRP, MRP, OATP, OCT, etc.) can change the pharmacokinetics of drugs, affecting their activity. Polymorphism of RYR1, CACNA1S, MT-RNR1, VKORC1, and other genes encoding receptors targeted by drugs, and human leukocyte antigen (HLA) gene, may affect drug pharmacodynamics by modifying drug targets or changing the sensitivity of biological pathways to pharmacological effects of medicines. Changes in drug pharmacokinetics and pharmacodynamics may cause DIDs аnd other ADRs. The use of pharmacogenetic tests will allow a personalised approach to patients’ treatment and prevention or timely detection of potential ADRs during therapy. Before prescribing some medicines, clinicians should use recommendations on their dosing based on pharmacogenetic tests, which are posted on the official websites of Pharmacogenomics Research Network (PGRN), Pharmacogenomics Knowledgebase (PharmGKB), and Clinical Pharmacogenetics Implementation Consortium (CPIC). The results of ongoing clinical studies on the effect of gene polymorphism on drug safety will soon allow for higher personalisation of the choice of pharmacotherapy and prevention of many ADRs, including DIDs

Clinical Signs and Medical History as Predictors of Enalapril-Associated Dry Cough in Cardiovascular Patients

Angiotensin-converting enzyme inhibitors (ACEIs) are among the most prescribed and effective medicinal products for the treatment of several cardiovascular diseases. According to a number of studies, 30% of patients taking ACEIs develop adverse drug reactions (ADRs), and treatment discontinuation is often required as a result. The most common ADR associated with ACEIs is a dry (non-productive) cough. Nevertheless, the clinical signs and medical history predictive of this ADR in cardiovascular patients are still understudied.The aim of the study was to analyse the clinical signs and medical history predictive of cough in patients with cardiovascular conditions treated with enalapril.Materials and methods. The study was carried out in 2019–2022 and enrolled 224 patients with essential hypertension (grades 2 and 3) treated with enalapril at a dose of 10–20 mg/day. The patients were assigned to 2 groups: Group 1 included 113 patients with enalapril-associated cough, while Group 2 (control group) comprised 104 patients without this ADR. At screening, all the patients underwent a general examination and a check of their allergy and medication history. Using the data obtained, the authors analysed the association of the clinical signs and medical history with the ADR of interest (dry cough).Results. In contrast to the control group, the group with ACEI-associated dry cough included more patients with a history of drug-induced toxicoderma (OR=5.639, CI 2.234–14.236, χ2=15.845, and p<0.001) or type 2 diabetes mellitus (OR=3.409, CI 1.461–7.953, χ2=8.7472, and p<0.01), a family history of bronchial asthma (OR=4.141, CI 2.066–8.299, χ2=17.417, and p<0.001), and a close family history of severe allergic reactions (OR=3.714, CI 1.720– 8.018, χ2=12.137, and p<0.001).Conclusions. A family history of allergy increases the probability of dry cough in patients taking ACEIs. In order to improve the safety of ACEI therapy, patients with cardiovascular conditions should be asked more detailed questions about their personal or first-degree family history of allergy

Effect of ABCB1 Gene Carriage and Drug-Drug Interactions on Apixaban and Rivaroxaban Pharmacokinetics and Clinical Outcomes in Patients with Atrial Fibrillation and Deep Vein Thrombosis

Aim. To investigate the effect of ABCB1 gene carriage and interdrug interactions on apixaban pharmacokinetics and clinical outcomes in patients with atrial fibrillation and deep vein thrombosis.Material and methods. Patients hospitalized at Yudin State Clinical Hospital participated in the study. A total of 92 patients (50 patients received apixaban and 42 – rivaroxaban) with non-valvular atrial fibrillation and deep vein thrombosis were included. Genotyping was performed by real-time polymerase chain reaction. Direct oral anticoagulants concentrations were measured using an electrospray ionization mass spectrometer in positive ionization mode.Results. In our study we found that in patients carrying the CT+TT ABCB1 (rs4148738) C>T genotype encoding the carrier protein (P-gp), the plasma concentration of rivaroxaban was statistically significantly higher p= 0.026. In addition, we found that patients taking apixaban together with a CYP3A4/P-gp inhibitor were 3.5 times more likely to have hemorrhagic complications than those without inhibitors p = 0.004.Conclusion. Our study revealed that the plasma concentration of rivaroxaban was higher in patients carrying the ABCB1 (rs4148738) C>T polymorphism T allele. And patients taking apixaban together with CYP3A4/P-gp inhibitor had higher risk of hemorrhagic complications in comparison with patients not taking such drugs. Further studies are needed on the influence of pharmacogenetics and pharmacokinetics on the safety and efficacy profile of apixaban and rivaroxaban, taking into account the trend of systemic approach to optimization of anticoagulant therapy of direct oral anticoagulants based on pharmacokinetic, pharmacogenetic biomarkers

The prevalence of serological markers of viral hepatitis among labor migrants arriving in the Russian Federation

Aim. To determine of the prevalence of viral hepatitis A, E, B, C and D markers in migrant workers.Materials and methods. Blood serum samples from 1,333 migrant workers recently arrived in Russia from Uzbekistan (n = 464), Tajikistan (n = 415), Ukraine (n = 308) and Moldova (n = 146) were analyzed. Anti-HAV IgG, anti-HEV IgM and IgG, HBsAg, anti-HBV and anti-HCV were tested using commercial ELISA tests.Results. The frequency of HBsAg detection was significantly higher among migrants from Tajikistan and Uzbekistan (5,3% and 5,2%, respectively) compared to migrants from Ukraine (1,0%) and Moldova (3,4%). No anti-HDV was detected in any positive HBsAg sample. The rate of anti-HCV detection was high regardless of the country of origin: 4,5% (Uzbekistan), 4.8% (Tajikistan), 3,9% (Ukraine), 4,8% (Moldova). Anti-HEV IgG was significantly higher in migrants from Uzbekistan and Tajikistan compared to those from Ukraine and Moldova (25,4% and 43,1%, vs. 7,8% and 12,3%, respectively, p <0,05). Anti-HEV IgM, indicative of current or recent infection, was detected in migrants from Uzbekistan, Tajikistan, Ukraine and Moldova with similar frequency – 3,9%, 7,8%, 5,8% and 6,8%, respectively. AntiHAV IgG positivity rate was significantly lower in migrants from Ukraine compared to those from Moldova, Uzbekistan and Tajikistan (70,1% versus 91,8%, 98,7%, 99,8%, respectively, p <0,05).Conclusion. The high prevalence of hepatitis B and C serologic markers in labor migrants, as well as anti-HEV IgM, suggests a high probability of the importation of HCV, HBV and HEV in the Russian Federation. Thus, inclusion of hepatitis B, C and E testing into routine screening of labor migrants might be beneficial

Dissipative continuous Euler flows

We show the existence of continuous periodic solutions of the 3D incompressible Euler equations which dissipate the total kinetic energy

Statin-Induced Myopathy

Scientific relevance. Being the main class of medicinal products for dyslipidaemia treatment, statins are widely used in clinical practice in various patient populations. However, statins can cause statin-associated muscle symptoms (SAMS), which are the most frequent and, in some cases, even life-threatening adverse reactions associated with these medicinal products.Aim. The study aimed to perform a systematic review of the epidemiology, classification, and physiological pathogenesis of SAMS, risk factors for this complication, and clinical guidelines for primary care physicians regarding the identification and treatment of patients with SAMS.Discussion. SAMS is an umbrella term that covers various forms of myopathies associated with satin therapy. According to the published literature, the prevalence of SAMS varies considerably and may depend on the study design, inclusion criteria, and the medicinal product used. SAMS has multiple putative pathogenic pathways that include genetically determined processes, abnormalities in mitochondrial function, defects in intracellular signalling and metabolic pathways, and immune-mediated reactions. The main known risk factors for developing SAMS include high-dose statins, drug–drug interactions, genetic polymorphisms, female sex, older age, Asian race, history of kidney, liver, and muscle disease, and strenuous physical activity. Given the lack of universally recognised algorithms for diagnosing SAMS, clinicians should consider the clinical presentation and the temporal relationship between statin therapy and symptoms. Other factors to consider include changes in muscle-specific enzyme levels and, in some cases, the results of blood tests for antibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase.Conclusions. To ensure the safety of statin therapy, it is essential to raise clinicians’ awareness of the risk factors for SAMS, indicative clinical and laboratory findings, and the need for dynamic patient monitoring, including the involvement of clinical pharmacologists

Фитофармакология: у истоков фармации и клинической фармакологии

Article is devoted to historical review of pharmacology and pharmacy herbal medicines since ancient times.Статья посвящена историческому обзору развития фармакологии и фармации растительных лекарственных препаратов с древних времён

Efficiency of treatment of laryngopharyngeal reflux with proton pump inhibitors depending on the <i>CYP2C19</i> polymorphism

Introduction. A treatment for LFR for many years, the superiority of PPIs over placebos is still controversial. Of particular clinical importance is the metabolic rate of PPIs in hepatocytes using the cytochrome P450 system with the participation of the isoenzyme CYP2C19 and partially CYP3A4Аim. We set a goal to study the efficacy of omeprazole 20 mg in the treatment of LFR symptoms without esophageal syndrome in patients with gastroesophageal reflux (GERD), depending on the polymorphism of the CYP2C19 genotype.Мaterials and мethods. After the exclusion criteria, 100 people took part in the study, 94 people completed the study.Results. According to the results, 26.6% of patients in the study group (residents of the Moscow region) with LFR symptoms without esophageal syndrome belong to fast metabolizers of CYP2C19, 4.2% to ultrafast metabolizers, 52.1% to normal metabolizers, 16% to intermediate metabolizers and 1.1% to slow CYP2C19.Conclusions. In patients with a rapid metabolism, within 1 month after discontinuation of omeprazole, it is necessary to increase the amount of omeprazole 20 mg intake up to 2 times a day in the morning and in the evening and reduce the duration of treatment to 6 weeks

Влияние полиморфизмов генов CYP2D6 и CYP2C9 на клиническую эффективность трамадола и кеторолака при использовании протокола ускоренного восстановления у пациентов с неосложненным острым калькулезным холециститом, перенесших холецистэктомию

Relevance. One of the key components of the accelerated recovery protocols (ARP), in addition to minimizing the surgical approach, is an adequate postoperative analgesia. Despite this, applied postoperative analgesia combinations are not devoid of drawbacks, such as lack of effective postoperative analgesia and the presence of side effect. The use of a pharmacogenetic approach to analgesic therapy for the purpose of its personalization may increase the effectiveness and safety of the use of analgesics. In particular, the presence of an inactive CYP2D6*4 allele , in which the conversion of tramadol to its active metabolite is reduced, contributes to the insufficient efficacy of the drug. As for non-steroidal anti-inflammatory drugs, the presence of CYP2C9*2/*3 polymorphisms leads to a decrease in drug metabolism and a longer half-life, resulting in the increase of the clinical effect and the risk of adverse reactions. Thus, genotyping of patients with the determination of the presence of specific genetic factors can rationalize the postoperative analgesia.Aim of study. Evaluation of the possible association of polymorphisms of the CYP2D6 and CYP2C9 genes with the clinical efficacy of tramadol and ketorolac in relation to postoperative pain.Material and methods. This observational clinical study involved 107 patients with uncomplicated acute calculous cholecystitis who underwent videolaparoscopic cholecystectomy and perioperative treatment according to ARP. All patients underwent whole blood sampling followed by real-time polymerase chain reaction genotyping. Analgesic efficacy was assessed using a visual analog scale (VAS) and McGill Pain Questionnaire.Results. In CYP2D64* carriers pain was higher than that of wild-type carriers, according to VAS and McGill Pain Questionnaire in all investigated periods. In carriers of CYP2C9*2, the pain syndrome was lower than in carriers of the wild type at all intervals studied. In carriers of CYP2C9*3 pain was lower only after 2 and 6 hours, also according to McGill Pain Questionnaire.Conclusion. 1. The presence of the polymorphic marker CYP2D6*4 may reduce the efficacy of postoperative tramadol analgesia compared with wild type. 2. The presence of the polymorphic marker CYP2C9*2 and CYP2C9*3 may increase the efficacy of ketorolac pain relief compared to wild type.Актуальность. Одним из ключевых компонентов всех протоколов ускоренного восстановления (ПУВ), помимо минимизации операционного доступа, является адекватная послеоперационная аналгезия. Несмотря на это применяемые комбинации послеоперационного обезболивания не лишены недостатков, таких как недостаточно эффективная послеоперационная аналгезия и наличие побочных эффектов от используемых препаратов. Применение фармакогенетического подхода к обезболивающей терапии с целью ее персонализации может повысить эффективность и безопасность применения анальгетиков. В частности, наличие неактивного аллеля CYP2D6*4, при котором снижено преобразование трамадола в его активный метаболит, способствует недостаточной эффективности препарата. Что касается нестероидных противовоспалительных препаратов, наличие полиморфизмов CYP2C9*2/*3 приводит к снижению метаболизма лекарств и более длительному периоду полувыведения, вследствие чего может усилиться клинический эффект и повыситься риск нежелательных реакций. Таким образом генотипирование пациентов с определением наличия конкретных генетических полиморфизмов может рационализировать послеоперационную аналгезию.Цель. Оценка возможной ассоциации полиморфизмов генов CYP2D6 и CYP2C9 с клинической эффективностью трамадола и кеторолака в отношении послеоперационной боли.Материал и методы. В этом обсервационном клиническом исследовании принимали участие 107 пациентов с неосложненным острым калькулезным холециститом, которым выполняли видеолапароскопическую холецистэктомию и проводили периоперационное лечение согласно оптимизированному ПУВ. Всем пациентам осуществлялся забор цельной крови с последующим генотипированием методом полимеразной цепной реакции в режиме реального времени. Обезболивающая эффективность оценивалась при помощи визуальной аналоговой шкалы (ВАШ) и опросника боли Мак-Гилла.Результаты. У носителей CYP2D6*4 болевой синдром был выше, чем у носителей дикого типа, по данным ВАШ и болевого опросника Мак-Гилла во все исследуемые промежутки. У носителей CYP2C9*2 болевой синдром был ниже, чем у носителей дикого типа во все исследуемые промежутки. У носителей CYP2C9*3 болевой синдром был ниже только через 2 и 6 часов, а также по данным оценочной шкалы боли Мак-Гилла.Выводы. 1. Наличие полиморфного маркера CYP2D6*4 может снизить эффективность послеоперационного обезболивания трамадолом по сравнению с диким типом. 2. Наличие полиморфного маркера CYP2C9*2 и CYP2C9*3 может повысить эффективность обезболивания кеторолаком по сравнению с диким типом