Pregabalin’s effect on human genetic material: in vitro study

Purpose of the study: Pregabalin is a prescription drug approved for the treatment of generalized anxiety disor­der; partial epilepsy; neuropathic pain and fibromyalgia. It is an alpha-2-delta ligand, structurally related to the neurotransmitter GABA that inhibits calcium currents via high-voltage-activated channels containing the a2d-1 subunit.Aim of the present study was to investigate the in vitro effect of pregabalin on healthy human cultured lymphocytes, by esti­mating three sensitive cytogenetic indices: Sister Chromatid Exchanges (SCEs), Proliferation Rate Index (PRI) and Mitotic Index (MI).Methods: SCEs are considered as one of the most sensitive markers of genotoxicity, whereas PRI is one of the most reli­able markers of cytostatic activity and MI shows precisely the ability of the cell to proliferate. We prepared eight pregabalin solutions commonly used in clinical practice. The solutions were added to cultures of peripheral blood lymphocytes taken from two young healthy donors. After 72 hours of incubation with the appropriate technique the cultured lymphocytes were plated on glass slides, stained with the Fluorescence plus Giemsa method and the above indices were estimated with the optical microscope.Results and Conclusions: Pregabalin at therapeutic doses exhibited dose-dependent cytogenetic activity in vitro, increasing SCE frequencies and diminishing PRI levels in normal human lymphocyte cultures. Interestingly, the variation of the magni­tude of MI reduction seems to be directly related to the decrease of PRI values as well as to the increase of SCE frequencies. Considering that the use of pregabalin is rapidly increased, further studies in other cell lines and in in vivo experimental settings are needed in order to evaluate its effect on genetic material

Significant Increase in Antibody Titers after the 3rd Booster Dose of the Pfizer-BioNTech mRNA COVID-19 Vaccine in Healthcare Workers in Greece.

The aim of our study was to assess the immunogenicity of the third dose of the BNT162b2 mRNA COVID-19 vaccine (Comirnaty) in a cohort of 129 health-care workers in Greece whose anti-S1 RBD IgG titers were monitored over the course of nine months. Titers were measured for each participant just before the third dose (nine months after the second dose) and also one month after the third dose. Of the 129 participants, 19 had been previously infected before starting the vaccination scheme. The SARS-CoV-2 IgG II Quant assay on the Architect System was employed to longitudinally assess the titers of IgG against the receptor-binding domain of the S1 subunit of the spike protein (anti-S1 RBD). Boosters raised Geometric Mean Concentrations (GMCs) by a factor of approximately 47 relative to levels at 9 months and by a factor of approximately 23 relative to levels at 6 months. The immune response one month after the third dose was significantly higher than the response achieved one month after the second dose (p = 0.008). In conclusion, our findings verify the potent immunogenicity elicited by the third dose in all age and prior COVID-19 status groups, suggesting that the timely administration of the third (booster) dose maximizes the immunogenic potential of the vaccine

Pharmacodynamic and pharmacokinetic properties of the novel antidepressant vortioxetine

Η βορτιοξετίνη είναι ένα νέο αντικαταθλιπτικό φάρμακο το οποίο, πέραν της αναστολής που προκαλεί στον μεταφορέα της σεροτονίνης, αλληλεπιδρά με διάφορους τύπους υποδοχέων της σεροτονίνης και γι’ αυτό το λόγο έχει χαρακτηριστεί ως διαμορφωτής και διεγέρτης των υποδοχέων της σεροτονίνης. Η παρούσα εργασία αποτελεί μια σύντομη ανασκόπηση πρόσφατων δεδομένων σχετικών με τη φαρμακοδυναμική, τη φαρμακοκινητική και την κλινική χρήση του φαρμάκου αυτού.Vortioxetine is a novel antidepressant which exhibits multi modal activity; in addition to inhibiting the serotonin transporter (SERT) it interacts directly with various types of 5-HT receptors and is thus classified as a serotonin modulator and stimulator (SMS). This is a short update of recent findings concerning vortioxetine’s pharmacodynamics, pharmacokinetics and clinical use

USE OF NOVEL PSYCHOACTIVE SUBSTANCES (NPS) OF NATURAL ORIGIN: AN INTERNATIONAL SURVEY

Aim NPS recreational use are mostly derived and modified from constituents of natural origin. Here we investigated the motivation of natural NPS use, perception of potential associated health risks and demographic factors associated with natural NPS use. Methodology The Bristol Online Survey was in English and advertised on the drug forum Bluelight and social media Facebook pages and via University email between 1 July and 17 November 2018 (812 responses; 458 NPS users). This pharmacoepidemiologic study was evaluated using SPSS software (IBM SPSS Statistics version 24;MacOS Sierra 10.12.3). Results The main motivation (67%) for natural NPS use was curiosity to ‘’experience something new and different’’ with a low perception of health risk (85%). The preferred natural NPS was magic mushrooms (psilocybin, 95%) often in combination with cannabis (63%). Gender, living area, educational background, smoking frequency and employment significantly affected (P<0.001) natural NPS use. Male respondents, residents of suburban and rural areas, smokers and respondents with low educational level represented the majority of natural NPS users as well as the employed, the unable to work and retired groups. Similarly, sexual orientation significantly affected (p<0.05) natural NPS use. Conclusion Users’ low perception of natural NPS safety profile and the fact that natural NPS use correlates with a lower level of education, indicates a need for enhanced statutory targeted prevention interventions in schools. Many users (67%) reported natural NPS make them happier and more optimistic about life emphasizing the need to study the potential application of these substances in appropriate clinical settings for therapeutic purposes in mental health.Peer reviewe

The effect of biologic agents currently used for rheumatoid arthritis on the central nervous system of healthy rats

The aim of this study was to investigate the development of behavioral and memory disorders on healthy adult rats, after chronic, systematic administration of methotrexate and the biologic agents, Tocilizumab (anti-IL6) and Infliximab (anti-TNFa), that are used for Rheumatoid Arthritis. 35 adult male Wistar rats, 12 weeks old, were used in this study. The rats were divided into 5 groups (n=7): a control group (CTRL), which was submitted to tests without receiving any drug, a placebo group (PLC) which received normal saline (i.p.), a methotrexate group (MTX) receiving 0.25mg/kg of the drug (i.p.), an infliximab group (INFL) receiving 6mg/kg of the drug (i.p.), and a tocilizumab group (TCZ) receiving 8mg/kg of the drug (i.p.). The drug infusion was performed weekly. After 30 days of drug administration, behavioral tests were performed to assess the rats’ stress levels and memory. The performed behavioral tests were (1) the Elevated-plus maze test, (2) the Elevated-zero maze test and (3) the Olfactory social memory test. The results were analyzed using Oneway-ANOVA and Kruskal-Wallis tests through SPSS 25.0. The MTX group spent significantly less time in the open arms of the mazes, compared to the CTRL group (P<0.001) and the PLC group (p=0.05), and needed less time during the second encounter compared to the first, when assessed in the olfactory social memory test (p=0.002). The TCZ and INFL groups spent more time in the open areas of both mazes compared to PLC and MTX groups (p=0.033). Based on the results of this study, the administration of biologic agents improves stress levels and shows a potentially anxiolytic effect, without significantly affecting memory

Nonmedical Use of Prescription Drugs among Medical Students and the Relationship With Illicit Drug, Tobacco, and Alcohol Use

Nonmedical use of prescription medications is a growing health problem including not only the opioid painkiller overdose epidemic but also benzodiazepine and stimulants misuse. Medical students express considerable high percentages of prescription drug misuse but also of illicit drug use, with cannabis being the frequently used illicit drug. We report the final results of a cross-sectional study among medical students that examined prevalence and motivation for use and suggest that medical students display similar patterns of misuse, for both licit and illicit drugs, to other students. Furthermore, a correlation was found between illicit drugs use with tranquilizers misuse and between smoking and alcohol misuse with opioids, sleeping drugs, and stimulants use. Considering that substance use during medical school affects students’ personal and professional lives and has potential consequences for their patients, further studies are needed to elucidate the prevalence but also the motivation for that use

Prevalence of use of on-label and off-label psychotropics in the Greek pediatric population

With a global increased use of psychotropics in pediatrics, their off-label use is a concern due to uncertainty and risk. Data on psychotropics use in the Greek pediatric population do not exist to date. We analyzed retrospective data from the nationwide pharmacy claim database, to estimate the prevalence of psychotropics in pediatrics focusing on off-label use (March 2016-October 2019). In total 63,782 pediatric subjects had at least one identified psychotropic prescription. The prevalence of psychotropics use was 5.1-14.6/1,000 pediatric inhabitants. When excluding 42,508 subjects who received only short-time hydroxyzine, the prevalence was 3.1-6.5/1,000 pediatric inhabitants; adolescents and boys had higher exposures. An in-depth analysis of 21,274 subjects accounting for 222,307 psychotropic dispensations, showed antiepileptics as the most frequent psychotropics, consistently with the finding on epilepsy being the most frequent diagnosis; diazepam was the single drug with the highest exposure in almost all ages. 14% of subjects have received at least one medicine with no pediatric information in the labelling, corresponding to 5.5% of dispensed psychotropics. 7.6% of all dispensed psychotropics were used in a non-authorized age range with quetiapine being the most frequent psychotropic as off-label age range; antipsychotics and antidepressants were first as off-label for non-authorized indication. Data from Greece show that a relevant number of patients are prescribed psychotropics, with 1 in 7 being under off-label use. Due to the limitations inherent to pharmacy claims databases, further research using clinical data for a longer follow-up period could confirm and identify trends in psychotropics use in Greece