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

Приверженность вакцинации различных слоев населения: результаты анкетирования

Voluntary anonymous questioning of groups of parents (n = 120), students of junior and senior courses of medical faculty (n = 250), оutpatient doctors (n = 45) concerning vaccination is carried out.Parents showed a generally positive (60%) attitude to vaccination, high anxiety (90%) in connection with the possible development of post-vaccination complications, as well as lack of awareness and inertia in acquiring knowledge about vaccination. The positive trend in knowledge among students from junior to senior courses is adjacent to the lack of practical orientation on vaccination. Outpatient doctors are cautious about vaccination, especially for children with chronic illnesses.Проведено добровольное анонимное анкетирование родителей (n = 120), студентов младших и старших курсов лечебного факультета медицинского университета (n = 250), врачей амбулаторного звена (n = 45) по вопросам вакцинации.Среди родителей выявлено в целом положительное (60%) отношение к вакцинации, тем не менее присутствует высокая тревога (90%) в связи с возможным развитием поствакцинальных осложнений, а также отмечена недостаточная информированность и инертность в приобретении знаний по вопросам вакцинации. Среди студентов выявлена положительная тенденция в приобретении теоретических знаний о вакцинопрофилактике от младших курсов к старшим, однако среди них отмечена недостаточная практическая ориентированность. Врачи амбулаторного звена с осторожностью относятся к вакцинации, особенно детей с хроническими заболеваниями

Sex peptide receptor-regulated polyandry mediates the balance of pre- and post-copulatory sexual selection in Drosophila

Polyandry prolongs sexual selection on males by forcing ejaculates to compete for fertilisation. Recent theory predicts that increasing polyandry may weaken pre-copulatory sexual selection on males and increase the relative importance of post-copulatory sexual selection, but experimental tests of this prediction are lacking. Here, we manipulate the polyandry levels in groups of Drosophila melanogaster by deletion of the female sex peptide receptor. We show that groups in which the sex-peptide-receptor is absent in females (SPR-) have higher polyandry, and – as a result – weaker pre-copulatory sexual selection on male mating success, compared to controls. Post-copulatory selection on male paternity share is relatively more important in SPR- groups, where males gain additional paternity by mating repeatedly with the same females. These results provide experimental evidence that elevated polyandry weakens pre-copulatory sexual selection on males, shifts selection to post-copulatory events, and that the sex peptide pathway can play a key role in modulating this process in Drosophil

Sperm transfer or spermatangia removal: postcopulatory behaviour of picking up spermatangium by female Japanese pygmy squid

In the Japanese pygmy squid Idiosepius paradoxus, females often pick up the spermatangium using their mouth (buccal mass) after copulation. To examine whether the female I. paradoxus directly transfers sperm into the seminal receptacle via this picking behaviour, or removes the spermatangium, we conducted detailed observations of picking behaviour in both virgin and copulated females and compared the sperm storage conditions in the seminal receptacle between females with and without spermatangia picking after copulation in virgin females. In all observations, elongation of the buccal mass occurred within 5 min after copulation. However, sperm volume in the seminal receptacle was not related to spermatangia picking. Observations using slow-motion video revealed that females removed the spermatangia by blowing or eating after picking. These results suggest that picking behaviour is used for sperm removal but not for sperm transfer. Moreover, the frequency of buccal mass elongation was higher in copulated females than in virgin females, consistent with the sequential mate choice theory whereby virgin females secure sperm for fertilisation, while previously copulated females are more selective about their mate. Female I. paradoxus may choose its mate cryptically through postcopulatory picking behaviour

Experience of Tizol gel administration for local therapy of rheumatoid arthritis

Objective. To assess efficacy, tolerability and safety of 1% Tizol gel in monotherapy and in combination with diclofenac (0,5%) and hydrocortisone (0,05%) in rheumatoid arthritis (RA). Material and methods. 88 RA pts with exudation in damaged joints were included in the study. They were randomized into 3 groups. Group I (30 pts) received local therapy with 1% Tizol gel. Group U (30 pts) - a complex drug contained 1% Tizol, diclofenac 0,5% and hydrocortisone 0,05%. Group 111 served as control and was treated locally with 1% diclofenac gel (Hiperion S.A., Rumania). Preparations were administered as thin layer on the whole surface of the inflamed joint trice a day for 14 days. Efficacy was assessed after the course of treatment. Pain intensity (VAS), joint circumference and functional impairment degree (WOMAC index) were used as outcome measures. Laboratory examination included complete blood count, hepatic enzymes level and urinanalysis. Results. Local therapy provided decrease of pain and joint circumference, increase mobility and allowed to diminish NSAID dose. Good effect was achieved in group I and II (53% and 60% respectively). Local effect of the drug in group 1 lasted in average 2,5 hours according to pts' opinion. Tolerability of the local therapy was good in ail pts. Systemic adverse events were absent. Conclusion. 1% Tizol gel and its combination with diclofenac (0,5%) and hydrocortisone (0,005%) are effective for local therapy of RA, decrease pain and inflammation in damaged joints. They can be used for treatment of inflammatory joint diseases particularly in pts with concomitant gastrointestinal diseases, hypertension absence of possibility of oral administration of NSAIDs and/or necessity of decrease of their dose