Department Of Clinical Pharmacology Research Articles

Criteria-based assessment of analgesic activity of condensed 3-aminothieno[2,3-b]pyridines and 1,4-dihydropyridines derivatives based on dataexperimental studies

BACKGROUND: An urgent task in pharmacology is to identify highly effective drugs with analgesic and anti-inflammatory activity. Heterocyclic cyanothioacetamide compounds are of considerable interest. Most authors evaluate the results of studies with separate private indicators of analgesic activity, and their comprehensive criterion assessment is insufficiently defined.
 AIM: Development of a criterion assessment in the study of analgesic activity and the establishment of its generalized criteria for samples of chemical compounds of medicinal products.
 MATERIALS AND METHODS: The experiments were performed on 390 male rats weighing 250–280 g in the laboratory of the Department of Fundamental and Clinical Pharmacology of St. Luke Lugansk State Medical University. Intact, control and reference (comparison group) groups of ten animals in each group were formed for each pharmacological test. In the intact group, the rats were unharmed. The control group received 2 mL of 0.9% sodium chloride solution intragastrically before each pharmacological test to establish analgesic activity. The reference group was injected with sodium metamizole at a dose of 7 mg/kg intragastrally once 1.5 h before modelling an acute pain reaction. Ten experimental groups were also formed, in which rats were injected with appropriate samples of new original studied derivatives of condensed 3-aminothieno[2,3-b]pyridines and 1,4-dihydropyridine intragastrically at a dose of 5 mg/kg 1.5 h before modelling acute pain syndrome. Tests for orofacial trigeminal pain, thermal immersion and hot plate were simulated. The indicators of the analgesic effect were the frequency of scratching movements in the orofacial trigeminal pain test and a statistically significant increase in the latent reaction period after the administration of the studied substances in the thermal immersion tests of the tail and hot plate.
 RESULTS: The studied samples with ciphers AZ-023, AZ-331 and AZ-383 showed maximum analgesic activity. The proposed criterion of analgesic activity in the experimental groups receiving thienopyridine derivatives with the AZ-023 cipher, according to the results of three tests, was 50.1, exceeding the indicator in the comparison group by 42 times. The values of this criterion in the experimental groups that received new 1,4-dihydropyridine derivatives with laboratory ciphers AZ-331 and AZ-383 for preventive purposes were the maximum in this series of experiments (64.3 and 68.4), which is 53–57 times higher than that of sodium metamizole.
 CONCLUSION: The methodology for assessing analgesic activity can be improved based on a criteria-based approach with the aggregation of particular indicators into an abstract model that allows quantifying the degree of analgesic activity. An integral criterion for the analgesic activity of cyanothioacetamide derivatives based on experimental data is proposed. In the future, the proposed approach can be used in studies of various analgesic samples.

IN MEMORY OF PROFESSOR YAREMA TOMASHEVSKYI – SCIENTIST, DOCTOR AND TEACHER

We are deeply saddened to inform that on August 12, Yarema Illich Tomashevskyi, a distinguished professor of the Danylo Halytsky Lviv National Medical University, passed away at the age of 94.
 Professor Tomashevskyi was born on December 3, 1929, in the village of Stetseva in Pokuttia area. In 1953, he graduated with honors from Lviv Medical Institute and then studied in the clinical residency program for internal medicine from 1953 to 1955. In the following three years, he chaired the therapeutic departments of Kamianka-Buzka District Hospital and the 4th Hospital in Lviv. In 1958, he commenced employment as an assistant at Lviv Medical Institute and was subsequently promoted to Associate Professor of therapeutic departments. He started and chaired the Department of Endocrinology and Clinical Pharmacology, where he worked for 44 years, from 1978 to 2022. Yarema Illich created and developed the Lviv endocrinological school, the regional endocrinological dispensary, and headed the regional association of endocrinologists. He was a member of the Ukrainian Scientific Society of Endocrinologists.
 Professor Tomashevskyi’s scientific and research endeavors are centered around the issues of cardiology, rheumatology, gastroenterology, balneotherapy, clinical vitaminology, and endocrinology. He deemed the prevention of diseases to be of paramount significance. He founded the Academy of Preventive Medicine at the Shevchenko Scientific Society. He has worked on programs aimed at preventing iodine deficiency disorders and early diagnosis of diabetes, which he diligently implemented in practice. Professor Tomashevskyi is the author and co-author of over 350 publications, including seven monographs and textbooks and many methodological recommendations. Under his leadership, two doctoral and 15 candidate theses were successfully defended.
 The professor’s professional activities included membership in the Ukrainian Medical Association, the European Association for the Study of Diabetes, and editorial boards of the journals “Endocrinology” and “International Endocrinology Journal.” He also contributed to the compilation of scientific works “The Phenomenon of Human. Healthy lifestyle,” “Medical Collection of The Shevchenko Scientific Society.” He was a full member of the Shevchenko Scientific Society and headed the Medical Commission of the SSS for several years. He was respected and known in the medical scientific community of Ukraine. In 1985, Yarema Illich was awarded the badge “Excellence in Healthcare.”
 Professor Yarema Tomashevskyi was an excellent teacher and lecturer, a highly qualified doctor who was loved and respected by students, colleagues, and patients. He was a respected citizen. The professor led a respectable life full of tireless work and care. His favorite sayings from the ancient sacraments, which he steadfastly adhered to, were: “Rush to do good, as human life is fleeting; do everything in moderation; and never express anger.” He was always cheerful, smiling, and friendly.
 Eternal and bright be his memory!
 
 Chairman of the Medical Commission
 of Shevchenko Scientific Society,
 Doctor of Medicine, Professor Valentyna Chopyak

Features of the frequency distribution of alleles and genotypes of the IL5 gene polymorphism rs2069812 in various phenotypes of bronchial asthma of professional genesis

Despite the fact that occupational bronchial asthma has long been considered as a separate, independent disease, in recent years, more and more attention has been paid to its heterogeneity. Phenotyping of occupational asthma was initially based on identifying combinations of clinical characteristics of the disease, but now an increasing amount of data is emerging making it possible to understand the cause of clinical differences at the molecular genetic level. Thus, molecular genotyping opens up new opportunities in the search for a more targeted and personalized approach to the treatment of occupational bronchial asthma, as well as in the development of an individual strategy for its prevention. The purpose of the study is to determine genetic markers of the risk of developing occupational asthma under conditions of exposure to sensitizing substances by assessing the IL5 rs2069812 polymorphism. Materials and methods. The study was conducted on the basis of the Department of Occu pational Diseases and Clinical Pharmacology named after honored scientist of the Russian Federation professor V. V. Kosarev, FSBEI HE Samara State Medical University of the Ministry of Health of Russia, and the Department of Occupational Pathology, Regional Center of Occupational Pathology, SBHI SR Samara Medical and Sanitary Unit No. 5 of the Kirov District. The study was carried out on 170 patients with various phenotypes of occupational bronchial asth ma and 50 participants in the control group: group 1 (42 patients) — phenotype «occupational asthma, allergic form», group 2 (36 patients) — phenotype «occupational asthma, non-allergic form», group 3 (58 patients) — phenotype «occupational asthma — occupational chronic obstructive pulmonary disease», group 4 (34 patients) — phenotype «occupational asthma — metabolic syndrome», group 5 — control group (healthy), 50 participants. As part of the study of genetic predisposition to occupational bronchial asthma, IL5 rs2069812 polymorphism was determined. DNA samples were isolated from peripheral venous blood lymphocytes using phenol-chloroform extraction. Genotyping was performed by real-time polymerase chain reaction using primers and probes designed using PrimerQuest (Integrated DNA Technologies, Inc.). Results. Thus, for the first time, the genetic markers of the risk of occupational asthma under exposure to sensitizing substances, i.e. IL5 rs2069812 polymorphism, have been identified, which makes it possible to recommend the determination of this genetic marker during indepth periodic medical examinations of individuals working under conditions of exposure to sensitizing and irritating substances in the presence of clinical, functional, and immunological changes. Conclusion. The identified marker profiles of genotypes of occupational bronchial asthma can optimize the approach to diagnosis, treatment, and prevention of this pathology, as well as expand the range of criteria for predicting the course of the disease. When IL-5 polymorphism is detected during molecular genetic studies, patients need to be linked to care and undergo repeated pulmonary function tests once every 6 months and in-depth periodic medical exami nations in a specialized occupational pathology center with the mandatory participation of a pulmonologist, allergist/immunologist, and occupational pathologist, as well as with conducting extended functional and immunological studies once every 2 years.

Features of formation and prediction of professional burnout of doctors of surgical specialties

In the context of the COVID-19 pandemic, medical workers (MW) turned out to be the most vulnerable category of the population at risk of developing psychoemotional disorders.
 The study aims to establish the characteristics of the state of the psychoemotional sphere in doctors of surgical specialties of COVID-hospitals, multidisciplinary hospitals (MDH) during the COVID-19 pandemic, as well as outpatient clinics (OPC).
 We have examined the following groups of doctors: group 1 consisted of doctors of surgical specialties working in COVID‑hospital (n=61); group 2 consisted of doctors of surgical specialties working in a multidisciplinary hospital (n=58); group 3 consisted of doctors of surgical specialties working in the outpatient clinic (n=55); group 4 — the control group included employees of engineering, technical and economic specialties not related to work in medical organizations (n=190). The authors have evaluated the professional burnout syndrome using a questionnaire on the assessment of professional burnout "Maslach Burnout".
 The work of doctors of surgical specialties during the COVID-19 pandemic is associated with the impact on medical workers of a number of specific risk factors associated with the provision of medical care to infected patients, as well as with significant changes in work, regarding aspects related to organization, safety, which contribute to increased levels of anxiety, professional burnout, stress.
 The work of doctors of surgical specialties during the pandemic of the new coronavirus infection COVID-19, compared with doctors of multidisciplinary hospitals and outpatient doctors, is associated with an increase in the level of occupational stress, the level of professional burnout. It is necessary to continue research on the emotional state of medical personnel in order to timely carry out preventive treatment to preserve the health of medical workers.
 Ethics. The scientists conducted a study within the Framework of the complex topic of the Department of Occupational Diseases and Clinical Pharmacology named after Honored Scientist of the Russian Federation Professor V.V. Kosarev of Samara State Medical University "A systematic approach to early diagnosis, prevention and prediction of the impact of low-intensity production factors on the health of workers" (State registration number AAAA-A18-118122190069-6, registration date applications on 12/21/2018). The study was approved by the local ethics Committee of the Samara State Medical University of the Ministry of Health of the Russian Federation on 11/23/2021. Each participant in the study gave informed voluntary written consent to participate in the study and publish personal medical information in an impersonal form in the journal Occupational Medicine and Industrial Ecology.

Clinical Pharmacology and Infection Control Department in a Multidisciplinary Health Care Organization: Peculiarities of Work Organization

Clinical Pharmacology and Infection Control Department in a Multidisciplinary Health Care Organization: Peculiarities of Work Organization

On the occasion of the 100th anniversary of the birth of professor Vasily Alekseevich Danilin, the first head of the Department of Occupational Diseases, Samara State Medical University, and the creator of the occupational pathology service of the Samara Region

Professor V.A. Danilin (February 12, 1924 - August 3, 1984) was a founder of the Department of Occupational Diseases and Clinical Pharmacology named after professor Vladislav Vasilievich Kosarev, Samara State Medical University, honored scientist of the Russian Federation, a talented GP, clinician, and occupational pathologist, an excellent teacher, a veteran who went through a terrible war, a passionate researcher, a brilliant lecturer, a demanding mentor and leader, and an empathetic person.

Therapeutic Drug Monitoring of Tacrolimus in Tunisian Renal Transplant Patients during the Tuberculosis Infection: A Retrospective, Observational, Single-centre Analysis.

A retrospective, observational, single-center analysis was performed at the Department of Clinical Pharmacology (National Centre of Pharmacovigilance, Tunisia). We analyzed the database of patients who received TAC from 2009 until 2018. We included samples provided from renal transplant patients infected by Mycobacterium tuberculosis after transplantation. Trough blood levels (C0) were determined using an immunoassay analyzer. The Therapeutic Range (TR) of TAC was considered between 5 and 10 ng/mL. Pharmacokinetic parameters were compared between the period of co-administration of TAC/ATT (period A) and the period during which patients received only TAC (period B). Seven renal transplant patients treated by TAC were included. 41 samples were analyzed (16; period A, 25; period B). Only 6 % of C0 values were found within TR during period A, while this rate was 44% during period B. During period A, 88% of TAC C0 was under the lower limit of TR, indicating a high risk of transplant rejection. The mean C0 and C0/D were significantly lower during period A (3.11±1.53 ng/mL vs 7.11 ± 3.37 ng/mL; p = 0.001 and 33.06 ± 24.89 vs 83.14 ± 44.46; p = 0.0006, respectively), without difference in doses between periods. Considering the results of this study, clinicians are suggested to monitor TAC closely in this particular circumstance.

Novel 1,4-Dihydropyridine Derivatives as Potential Agents with Analgesic Activity IN Orofacial Trigeminal Pain Test: Experimental Preclinical Randomized Trial

Background. In the majority of cases, contemporary pharmacological correction mainly focuses on the most effective analgesia. Therefore, the search for and research into new analgesic drugs are a priority in modern pharmacology.Objective — to establish the level of analgesic activity in eight novel heterocyclic compounds of 1,4-dihydropyridine derivatives synthesized in a classic test of orofacial trigeminal pain in animal experiments.Methods. An experimental preclinical randomized trial of the analgesic activity in 1,4-dihydropyridine derivatives was carried out. The experiment was conducted on 100 white male outbred rats in the laboratory of the Fundamental and Clinical Pharmacology Department, St. Luke Lugansk State Medical University, Lugansk People’s Republic. Novel 1,4-dihydropyridine derivatives were preliminarily investigated in a virtual biological screening by means of Swiss Target Prediction tool (Swiss Institute of Bioinformatics, Switzerland). The laboratory animals were divided into a control group (rats were exposed to acute pain syndrome by injecting 0.1 ml of 5% formalin solution into the vibrissae area without pharmacological correction), a comparison group (rats which received metamizole sodium (OOO Farmstandard) at a dose of 7 mg/kg 1.5 hour prior to acute pain syndrome modeling in the vibrissae area), and eight experimental groups (1.5 hours before formalin administration, novel 1,4-dihydropyridine derivatives under study at a dose of 5 mg/ kg were intragastrically injected). 10, 15 and 20 minutes after simulating acute pain, the number of scratching movements of the forelegs around orofacial region per minute was counted. Statistical processing of the results involved methods of mathematical statistics for quantitative variability and was carried out using Statistica 12.5 (IBM, USA).Results. Animals treated with 1,4-dihydropyridine derivatives d02-133 and d02-172 under the experimental conditions showed a significant (13–21 times) decrease in scratching movements frequency by the 10th minute of observation in comparison with the control group. By 15th minute, the analgesic activity of the cyanothioacetamide derivatives increased 14 and 11 times as compared to these indicators of the reference group. After 20 minutes, the analgesic activity of these compounds in terms of inhibiting nociceptive impulses, as compared to the control group, was also high, as the number of scratching movements in the vibrissae area in animals of these experimental groups was 8–9 times lower than in control group. The orofacial trigeminal pain test detected the most exhibited analgesic activity in novel cyanothioacetamide derivatives d02-139, d02-133, and d02-172, which appeared to be higher than that of metamizole sodium.Conclusion. It was found that novel original derivatives of 1,4-dihydropyridine showed a high degree of analgesic activity.

Genotypes and frequencies of the TSLP gene variant rs1837253 in different occupational asthma phenotypes

Introduction. Currently, despite the fact that occupational asthma has long been considered as a separate, independent disease, recent studies pay more and more attention to its heterogeneity. Occupational asthma phenotyping was originally based on the identification of combinations of clinical characteristics of the disease, but now more and more data that allow understanding the cause of clinical differences at the molecular genetic level are emerging. Thus, molecular genotyping opens up new opportunities in the search for a more targeted and personalized approach to the treatment of occupational asthma, as well as in the development of an individual strategy for its prevention. The aim of the study was to determine the genetic risk markers for the development of oc cupational asthma under the influence of sensitizers by assessing the TSLP gene polymor phism rs1837253. Materials and methods. The study was conducted on the basis of the Department of Occupational Diseases and Clinical Pharmacology named after honored scientist of the Russian Federation professor V. V. Kosarev, FSBEI HE Samara State Medical University of the Ministry of Health of the Russian Federation, and the Department of Occupational Pathology, SBHI SR Samara Medical and Sanitary Unit No. 5 of the Kirovsky District. The study involved 170 patients with various phenotypes of occupational bronchial asthma (OBA) and 50 people in the control group: group 1 (42 people) — the phenotype «allergic occupational bronchial asthma», group 2 (36 people) — the phenotype «non-allergic occupational bronchial asthma», group 3 (58 people) — the phenotype «occupational bronchial asthma — occupational chronic obstructive pulmonary disease», group 4 (34 people) — the phenotype «occupational bronchial asthma — metabolic syndrome», group 5 (50 people) — the control group (healthy). As part of the study of genetic predisposition to occupational bronchial asthma,genetic polymorphisms of the rs1837253 TSLP gene were determined. DNA samples were isolated from peripheral venous blood lymphocytes by phenol-chloroform extraction. Genotyping was performed by real-time polymerase chain reaction using primers and probes developed with the PrimerQuest tool (Integrated DNA Technologies, Inc.). Results. Thus, for the first time, genetic risk markers for the development of occupational asthma under the influence of sensitizers have been identified: the TSLP gene polymorphisms rs1837253, which makes it possible to recommend determining these genetic markers during in-depth periodic medical examinations in persons working under exposure to sensitizing and irritating substances in the presence of clinical, functional, and immunological changes. Conclusion. The identified marker profiles of OBA genotypes can optimize the approach to the diagnosis, treatment and prevention of this pathology, as well as expand the range of criteria for predicting the course of the disease. If polymorphisms of the TSLP gene are detected during molecular genetic studies, patients need to be registered with a dispensary and require repeated examinations of the function of external respiration once every 6 months and in-depth periodic medical examinations in a specialized center of occupational pathology with the obligatory participation of a pulmonologist, an allergist-immunologist, an occupational pathologist, as well as conducting extended functional and immunological studies once every 2 years.

Evaluation of Stress Response in Middle-Aged Male Diabetic Hypertensive Patients.

Stress triggers a cascade of reactions that alter the organism's dynamic steady state. There is a scarcity of interventional studies that show cortisol variability upon stress over time in groups of patients with chronic noncommunicable diseases and comorbidities. We aimed to examine salivary cortisol changes in the cognitive stress response of patients with hypertension and diabetes mellitus (HT&DM) and patients with hypertension (HT) and to determine differences between them. The study was conducted using a stress test of solving an arithmetic task in 62 patients with HT&DM and HT who were being treated in the outpatient clinic of the Medical Pharmacology and Clinical Pharmacology Department in Istanbul University, Istanbul Medical Faculty Hospital. There was no statistically significant difference between the HT&DM and HT groups for systolic blood pressure (SBP) and diastolic blood pressure (DBP) values (P = .331 and P = .058). When measured by repeated ANOVA, salivary cortisol level [F (1.842, 60) = 8.771, P < .0001], SBP [F (2.185, 60) = 12.080, P < .0001], DBP [F (2.793, 60) = 6.043, P = .001], and heart rate [F (2.073, 60) = 13.259, P < .0001] were statistically significant for the main effect (time), while the effect of the group × time interaction factor was statistically not significant (P = .773; P = .751; P = .713 and P = .506, respectively). The arithmetic problem-solving task used with the HT&DM and HT patients was useful as an acute stress test in the laboratory environment. There was no statistically significant difference for group × time interaction factor between the HT&DM and HT groups; however, the salivary cortisol and BP values increased significantly after acute stress within each group.

Influence of Vitamin D Status and IL-10 Gene Promoter Polymorphism (rs1800871) on Plasma IL-10 Levels in Apparently Healthy Individuals from Southern India: A Cross-sectional Study

Introduction: Interleukin-10 (IL-10) is a major anti-inflammatory cytokine, which plays an important role in regulating inflammatory responses of the immune system. Changes in IL-10 level and its function can cause an imbalance in immune response, which can be associated with various disease conditions. Aim: To study the influence of vitamin D status and IL-10 gene promoter polymorphism (rs1800871) on circulating IL-10 cytokine levels in apparently healthy South Indian population. Materials and Methods: A cross-sectional study was conducted at the Department of Clinical Pharmacology, JIPMER, Puducherry, India from January 2016 to December 2017. Apparently healthy South Indian volunteers (N=101) of either sex, age more than 18 years, were recruited for the study, after obtaining written informed consent. Serum 25-hydroxy vitamin D and plasma IL-10 levels were measured by using Chemiluminescence and Enzyme Linked Immunosorbent Assay (ELISA), respectively. IL-10 rs1800871 genotyping was performed by Real Time-polymerase Chain Reaction (RT-PCR). Values were expressed as median, Interquartile Range (IQR) and proportions were described as number with percentage. Results: The median serum vitamin D and plasma IL-10 levels observed among the study population were 18.21 ng/ mL IQR, 11.3-23.08 ng/mL) and 9.04pg/mL (IQR, 7.75, 11.34 pg/mL) respectively. The genotype and allele frequencies of rs1800871 were consistent with that of the African, South Asian population of 1000 genome project. Plasma IL-10 levels were not significantly different across genotypes (p-value=0.091), even though the median level among homozygous mutant (TT) volunteers was observed to be less (8.35 pg/mL vs 9.69 pg/mL, 9.83 pg/mL). The correlation between vitamin D and IL-10 levels was observed to be insignificant (p-value=0.143). Conclusion: The present study has reported the rs1800871 genotype frequency, circulating serum vitamin D levels and plasma IL-10 levels in the apparently healthy South Indian population. IL-10 cytokine levels were not significant across the different genotype and vitamin D status groups. No significant correlation was observed between the IL-10 and vitamin D levels among the sample studied.

Treatment Reconciliation in Parkinson’s Disease Patients with Particular Reference to Wearing-off and Motor fluctuations: A Registry-based, Prospective, Observational Study

Introduction: Parkinson’s Disease (PD) is the second most frequent neurodegenerative disease and dopaminergic agents are frequently used as a treatment while ‘end of dose deterioration’ or ‘Wearing-Off (WO)’ phenomenon is common with these agents. Treatment reconciliation may be helpful in this situation and there is dearth of studies especially in India. Aim: To study the WO effects in patients of PD, their pharmacotherapy and outcome. Materials and Methods: This registry-based, prospective, observational, outcomes-based study was conducted in the Department of Clinical and Experimental Pharmacology, School of Tropical Medicine, Kolkata, West Bengal, India, in collaboration with Department of Neuromedicine of Kolkata Medical College and private clinics of a Neurologist from January 2020 to December 2021. An attempt was also undertaken to make a registry of Idiopathic Parkinson’s Disease (IPD) patients. WO Questionnaire 19-items (WOQ19), Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS Scale), The 39-items Parkinson’s Disease Questionnaire (PDQ-39 questionnaire), The 8-items Morisky Medication Adherence Scale (MMAS scale), suspected Adverse Drug Reaction (ADR) Reporting Form of Indian Pharmacoepia commission (version 1.3), World Health Organisation- Uppsala Monitoring Centre (WHO-UMC) Scale, Naranjo causality assessment scale, Hartwig and Seigel’s Severity Assessment Scale were used in the present study. The study was commenced after obtaining approval from institutional ethics committee. The data was then analysed with parametric or non parametric tests using (mean±Standard Deviation (SD), median, Fisher’s-exact test, Friedman’s Analysis of Variance (ANOVA) test, Wilcoxon matched pair signedrank test). Data collected and then statistically analysed by using WPS Excel version 2021 and GraphPad Prism version 9 software. Results: Total IPD patients were found to be 111 in the present study with a mean age of IPD patients as 61.85±7.20 years. Incidence of WO in the present study was found to be 40.5% among IPD patients. Most common characteristic of WO was found to be tremor in 104 (28.8%) patients followed by slowness of movement in 63 (17.5%) patients. WHO-UMC scale and Naranjo causality assesment scale both revealed 36.4% ADRs were probable category and 63.6% were possible category. MDS-UPDRS Score, PDQ-39 Score, MMAS-8 score significantly (p-value&lt;0.05) improved during the course of treatment. Conclusion: Dose adjustment of syndopa was mostly used in the management of WO phenomenon and significant improvement in the quality of life of the patients was seen.

Professor V. A. Danilin. Biography milestones (to the 50th anniversary of the Department of Occupational Diseases and Clinical Pharmacology, Samara State Medical University)

The article describes the main milestones of the biography of professor V. A. Danilin, PhD in Medicine.

Professor V. V. Kosarev and his role in the development of medical science and education to the 50th anniversary of the Department of Occupational Diseases and Clinical Pharmacology, Samara State Medical University

The article describes the main milestones of the life of professor V. V. Kosarev, PhD in Medicine, and his role in the development of medical science and education.

Case series of chronic spontaneous urticaria following COVID-19 vaccines: an unusual skin manifestation.

BackgroundUrticaria following the COVID-19 vaccine was rarely reported and had a short self-limited resolution. However, there has been relatively little literature published on CSU induced by COVID-19 vaccines.PurposeWe describe a case series of patients who experienced CSU after SARS-CoV-2 vaccination.MethodsA retrospective case series of 10 patients referred to the Department of Clinical Pharmacology of the University of Monastir (January 2021–January 2022) and included for evaluation of urticaria after COVID-19 vaccination.ResultsThe median age was 31 years and patients were mostly female. Atopy was presented in 3 patients and urticaria was accompanied by angioedema in 6 patients. The median time interval between vaccination and the onset of urticaria was 28.5 h. The offended dose was the first one in 8 patients. The resolution of the eruption was observed at least 2 months later, despite the regular use of a full dose of antihistamine in nine patients. Polynuclear leucocytosis was identified in 5 patients. Anti-TPOAb was positive in one patient after receiving the BNT162b2 vaccine. Total serum IgE was elevated in 4 patients. Skin tests for the suspected vaccine as well as the vaccine excipient were negative.ConclusionWe add to the medical literature ten new cases of chronic spontaneous urticarial reactions following COVID-19 vaccines uncontrolled with high-dose first-generation H1 antihistamines.

DRESS characteristics according to the causative medication.

To date, no study has identified a clear relationship between drug and a specific clinical presentation of DRESS. To investigate the particularities of DRESS and analyze the variation of DRESS pattern according to culprit drugs. We analyzed cases of DRESS notified to the Department of Clinical Pharmacology at the University Hospital of Monastir over a 15-year period. The statistical study was performed using the comparative and multivariate analysis. DRESS was mostly induced by anticonvulsive agents (27%) followed by allopurinol (26.3%) and antibiotics (24%): For anticonvulsive agents, the occurrence of lymphadenopathy was higher, renal involvement was rare and mild, and positive skin tests were more frequent. The allopurinol group was associated with the patient's older age and a lower incidence of lymphadenopathy and kidney injury. For antibiotics, eosinophilia rate was lower, time to recovery was shorter, and RegiSCAR score was low. The multivariate analysis showed a link of allopurinol with severe renal impairment, antibiotics with short latency period and low RegiSCAR score, and anticonvulsants with high propensity of positive skin test. We report the largest African and south Mediterranean cohort of DRESS and evaluated the usefulness of skin tests in identifying the culprit drug. The prominent finding was that latency period and renal involvement may independently differ according to culprit drugs.

Contrast Media Adverse Drug Reactions in Highly Polluted Environment.

Iodinated- (ICM) and gadolinium-based (GCM) contrast media are used in radiology imaging techniques, such as computer tomography (CT) and magnetic resonance (MR), respectively. The paper aims to analyze the adverse drug reactions of ICM and GCM on different sites of the body in a highly polluted environment. We analyzed the pharmacovigilance in contrast media on the basis of reports submitted to the Regional Center for Monitoring of Adverse Drug Reactions (ADR) at the Department of Clinical Pharmacology in Wrocław. Safety profiles were compared between different ICM and GCM and at the system organ level using the proportional reporting ratio (PRR). We analyzed 124 reports of adverse reactions related to contrast agents between 2006 and 2021. Our findings revealed that ADR combinations occurred more frequently after the use of iodinated contrast agents (72.08%) than gadolinium contrast agents (27.92%). Iomeprol and Iopromide were identified as the most frequently reported media. Each medium presented a different safety profile. Skin disorders are the most common adverse drug reactions among patients using both iodine- and gadolinium-based contrast media. Gadolinium-based contrast agents are characterized by similar organ toxicity. Conversely, iodine-based contrast agents are more diverse—some of which show tissue specificity, such as Iodixanol for the gastrointestinal system or Iohexol for the respiratory tract. This study shows relatively high occurrence of respiratory tract related ADRs in Wrocław. We also prove that it is possible to choose the most optimal contrast agent for patients with specific organ site problems to omit the possible complications.

Elevated Lp(a) and course of COVID-19: Is there a relationship?

BackgroundLipoprotein (a)–Lp(a) has proinflammatory, prothrombotic and proatherogenic properties and may theoretically influence the course of COVID-19.ObjectivesThe aim of the study was to explore whether patients hospitalized due to COVID-19 with Lp(a) ≥30mg/dl may develop a worse course of the disease, increased incidence of thromboembolic complications, intubation and ICU hospitalization or death.Patients and methodsA retrospective analysis was performed of 124 patients hospitalized due to COVID-19 in the Department of Internal Diseases and Clinical Pharmacology between 29 November 2020 and 15 April 2021. The only exclusion criterion was age≥80 years. Patients were divided into two groups: 1. COVID-19 patients with Lp(a) <30mg/dl regarded as not elevated n = 80; 2. COVID-19 patients with Lp(a) ≥30 regarded as elevated n = 44.ResultsA total of 124 COVID-19 patients were included in the study (66 men and 58 women) with a mean age of 62.8±11 years. COVID-19 patients with elevated Lp(a) level had significantly longer hospitalization time (11 vs. 9.5 days; p = 0.0362), more extensive radiological changes in CT scan (35 vs. 30%; p = 0.0301) and higher oxygen demand on admission (8 vs. 5L/min; p = 0.0428). Elevated Lp(a) was also associated with significantly higher OR for High Flow Nasal Oxygen Therapy (HFNOT) OR = 3.5 95%CI(1.2;8.9), p = 0.0140, Intubation and ICU OR = 4.1 95%CI(1.1;15.2) p = 0.0423, Death OR = 2.8 95%CI(0.9;8.5), p = 0.0409.ConclusionsElevated Lp(a) might be one of the factors which contribute to a more severe course of COVID-19; however, further studies including larger groups of patients are needed.

DRESS syndrome: Symptomatology according to the culprit drug

Introduction ( contexte de la recherche ) To date, no study has identified a clear relationship between drug and a specific clinical presentation of DRESS. Investigate the particularities of DRESS and analyze the variation of DRESS pattern according to culprit drugs. We analyzed cases of DRESS notified to the Department of Clinical Pharmacology at the University Hospital of Monastir over a 15-year period. Statistics was performed using comparative and multivariate analysis. For “anticonvulsive agents”, the occurrence of lymphadenopathies was higher, the renal involvement was rare and mild, and positive skin tests were more frequent. “Allopurinol” group was associated to a higher patients age, a lower occurrence of lymphadenopathies and severe renal impairment. For “antibiotics”, eosinophilia rate was lower, time to recovery was shorter and RegiScar score was weak. The multivariate analysis showed a linkage of allopurinol to severe renal impairment, antibiotics to short latency period and weak RegiScar score and anticonvulsants to high propensity of positive skin test. We report the largest African and south Mediterranean cohort of DRESS and evaluated the usefulness of skin tests in identifying the culprit drug. The prominent finding was that independently, latency period and renal involvement may differ according to culprit drugs.

Euthyroid Sick Syndrome as a Prognostic Indicator of COVID-19 Pulmonary Involvement, Associated With Poorer Disease Prognosis and Increased Mortality

ObjectiveThe prevalence of euthyroid sick syndrome (ESS) and its association with the prognosis of COVID-19 and mortality in patients with lung involvement in COVID-19 have not yet been elucidated. MethodsClinical and laboratory data of patients with COVID-19 with or without ESS were collected retrospectively and analyzed on admission. All subjects were admitted to the Department of Internal Diseases and Clinical Pharmacology at Bieganski Hospital between December 2020 and April 2021. ResultsIn total, 310 medical records of patients with COVID-19 were analyzed retrospectively. Among 215 enrolled patients, 82 cases of ESS were diagnosed. The patients with ESS had higher pro-inflammatory factor levels, longer hospitalizations, and a higher risk of requiring high-flow nasal oxygen therapy or intubation than the patients without ESS. The Kaplan-Meier curve indicated that the patients with ESS had a lower probability of survival when computed tomography showed ≤50% parenchymal involvement compared with that in patients without ESS. However, no differences in mortality were noted in those with more than 50% parenchymal involvement. The survival curve showed that ESS was associated with a higher risk of mortality during hospitalization. ConclusionESS is closely associated with a poor prognosis, including longer hospitalizations, more frequent intubation, transfer to the intensive care unit, and a higher mortality rate in patients with COVID-19. ESS is a potential prognostic predictor of survival, regardless of lung involvement in COVID-19.