Репозиторий Университета

© 2020 The Authors The increased diffusion of the so-called novel psychoactive substances (NPS) and their continuous change in structure andconceivably activity has led to the need of a rapid screening method to detect their biological effects as early as possible after their appearance in the market. This problem is very felt in forensic pathology and toxicology, so the preclinical study is fundamental in the approach to clinical and autopsy cases of difficult interpretation intoxication. Zebrafish is a high-throughput suitable model to rapidly hypothesize potential aversive or beneficial effects of novel molecules. In the present study, we measured and compared the behavioral responses to two novel neuroactive drugs, namely APINAC, a new cannabimimetic drug, and methiopropamine (MPA), a methamphetamine-like compound, on zebrafish larvae (ZL) and adult mice. By using an innovative statistical approach (general additive models), it was found that the spontaneous locomotor activity was impaired by the two drugs in both species: the disruption extent varied in a dose-dependent and time-dependent manner. Sensorimotor function was also altered: i) the visual object response was reduced in mice treated with APINAC, whereas it was not after exposure to MPA; ii) the visual placing responses were reduced after treatment with both NPS in mice. Furthermore, the visual motor response detected in ZL showed a reduction after treatment with APINAC during light-dark and dark-light transition. The same pattern was found in the MPA exposed groups only at the dark-light transition, while at the transition from light to dark, the individuals showed an increased response. In conclusion, the present study highlighted the impairment of spontaneous motor and sensorimotor behavior induced by MPA and APINAC administration in both species, thus confirming the usefulness of ZL as a model for a rapid behavioural-based drug screening.

© 2020 The Authors The increased diffusion of the so-called novel psychoactive substances (NPS) and their continuous change in structure andconceivably activity has led to the need of a rapid screening method to detect their biological effects as early as possible after their appearance in the market. This problem is very felt in forensic pathology and toxicology, so the preclinical study is fundamental in the approach to clinical and autopsy cases of difficult interpretation intoxication. Zebrafish is a high-throughput suitable model to rapidly hypothesize potential aversive or beneficial effects of novel molecules. In the present study, we measured and compared the behavioral responses to two novel neuroactive drugs, namely APINAC, a new cannabimimetic drug, and methiopropamine (MPA), a methamphetamine-like compound, on zebrafish larvae (ZL) and adult mice. By using an innovative statistical approach (general additive models), it was found that the spontaneous locomotor activity was impaired by the two drugs in both species: the disruption extent varied in a dose-dependent and time-dependent manner. Sensorimotor function was also altered: i) the visual object response was reduced in mice treated with APINAC, whereas it was not after exposure to MPA; ii) the visual placing responses were reduced after treatment with both NPS in mice. Furthermore, the visual motor response detected in ZL showed a reduction after treatment with APINAC during light-dark and dark-light transition. The same pattern was found in the MPA exposed groups only at the dark-light transition, while at the transition from light to dark, the individuals showed an increased response. In conclusion, the present study highlighted the impairment of spontaneous motor and sensorimotor behavior induced by MPA and APINAC administration in both species, thus confirming the usefulness of ZL as a model for a rapid behavioural-based drug screening.

© 2018, Dynasty Publishing House. All rights reserved. At present the incidence rates of urogenital chlamydiosis maintain the leading positions among sexually transmitted infections. Special attention to this infection is conditioned by a high risk for development of complications on the part of the reproductive system in both women and men. The ability of Chlamydia to affect various tissues accounts for a broad spectrum of clinical manifestations of urogenital pathologies: urethritis, vulvovaginitis, cervicitis, endometritis, salpingitis, epididymitis, prostatitis, proctitis, and also extragenital forms of disease. Taking into account a possibility of transition of Chlamydia infection into a latent stage with subsequent development of a chronic persisting course, early and adequate management of infection is of considerable importance. Etiotropic therapy of Chlamydia infection employs antibacterial drugs capable of penetrating into cells. Tetracycline antibiotics are the most effective drugs of choice administered as part of complex therapy. Minolexin is a tetracycline antibiotic that demonstrates the best effectiveness in the fight against infectious agents affecting the urogenital tract. The article presents the author’s clinical experience of using minolexin for management of urogenital chlamydiosis in 60 patients.

© 2018 Izdatel'stvo Meditsina. All rights reserved. Background: The widespread prevalence of infertility, the low effectiveness of assisted reproductive technologies (ART), and the high incidence of chronic endometritis (CE) in infertile women determine the relevance of the considered problem. The aim of the study was to determine the clinical and anamnestic, laboratory, and instrumental features of CE associated with infertility and unsuccessful IVF cycles in women of reproductive age. Materials and methods: The study enrollred 150 women of reproductive age with morphologically established CE (main group, n=120) and without CE (control group, n=30). A subgroup I of the main group included 64 patients with infertility and IVF failures, a subgroup II - 56 fertile women. In addition to anamnesis collection and identification of CE clinical features, all patients underwent infectious screening, immunological and immunohistochemical analysis, ultrasound examination of pelvic organs with dopplerometry, and office hysteroscopy. A comparative analysis of the data obtained from subgroups of the main group was conducted. Results: Histological study of endometrial pipelle-biopsy specimens on the 7-10th day of the cycle revealed CE in all patients of the main group. We found prevalence of mean duration of CE in the subgroup I relative to subgroup II - 5.5±0.06 years and 2.4±0.07 years, respectively (p<0.001). Infectious screening showed that 58 (90.6%) patients of the I subgroup had sterile endometrial seeding which was 16.9 times higher than in subgroup II (p<0.0001). Immunological analysis determined the presence of AEAT in all patients of the subgroup I, 43 of which (67.2%) were above 265 U/ml, while 51 (91.1%) of subgroup II had no AEAT (p<0.001). Immunohistochemical analysis of the endometrium on the 18th-24th day of the cycle established high expression of CD16, CD20, CD56, and HLADRII in 58 (90.6%) patients of the subgroup I, whereas in 54 patients (96.4%) of II subgroup high expression of CD16 and CD20 with low amount of CD56- and HLA-DRII-positive cells was registered (p<0.001). We determined prognostically significant clinical and anamnestic risk factors predisposing to the development of infertility in patients with CE (p<0, 05). We revealed certain echographic, dopplerometric, and hysteroscopic criteria of CE demonstrating the critical disruption of endometrial receptivity in infertile women. Conclusion: Most patients (90.6%) with infertility had autoimmune component of CE characterized by prolonged (more than 5 years) course, high serum level of AEAT, sterile endometrial crops, and high expression of inflammation markers CD16, CD20, CD56 and HLA-DRII .

© 2018 Media Sphera Publishing Group. All rights reserved. Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults and is classified as either primary (idiopatic) or secondary MN according to underlying etiology (the later result from some known disease such as systemic autoimmune diseases, infections, malignancies, drugs, etc). In recent years, phospholipase A2 receptor 1 (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) were identified as two major podocytic antigens involved in the pathogenesis of idiopatic MN (IMN). And the discovery of circulating antibodies specific for these target antigens has transformed the diagnostic workup and significally improved management of IMN. However why do such antibodies develop is not conclusively established. The role of underlying genetic factors is discussed. The review presents the results of recent studies, that have shown significant associations of specific genetic factors (particularly human leucocyte antigen class II and PLA2R1 genes) with IMN.

© 2018 The Authors. Published by Elsevier B.V. Identification of genes variants (alleles) in organisms can become a time-consuming task due to great diversity. Polymorphism is also a feature of HLA, the main complex of human histocompatibility. Errors in sequencing can also cause incorrect determination of alleles. The authors of the paper propose a method for analyzing high-performance sequencing data, which allows observing high accuracy in the problem of genotyping HLA.

© 2018 Media Sphera Publishing Group. All rights reserved. Objective. To clarify the association between HLA-DRB1 and TNFα (-308G>A) genes polymorphism and joint destruction/further progression during 12 months of the follow-up period (FUP) in patients with early (<6 months), active, predominantly antibodies to cyclic citrullinated peptide (ACCP) and rheumatoid factor (RF)-positive rheumatoid arthritis (RA) treated according to "Treat to target" strategy. Materials and Methods. The study included 85 patients with early RA and duration of symptoms <6 months. All patients were initially assigned to subcutaneous methotrexate (MTX) with rapid dose escalation to 20-25 mg/week. Combination MTX + biological therapy, mainly adalimumab, was used when MTX was ineffective. Joint destruction was assessed by Sharp-Van der Heijde modification scoring method at baseline and after 12 months FUP. Real time polymerase chain reaction (PCR-RT) was used for TNFα gene polymorphism (-308G>A) genotyping. Low resolution PCR-RT with subsequent sequence-based typing of ∗04 were performed to study HLA-DRB1 gene polymorphism. The HLA-DRB1∗01, ∗04:01, ∗04:04, ∗04:05, ∗04:08, ∗10 alleles were categorized as SE+ (Shared Epitope) alleles. Results. As for TNFα gene polymorphism, it was demonstrated that the number of narrowings and total Sharp score values were almost twice as high at baseline in GG genotype carriers as compared to GA genotype carriers (ρ<0,005, and ρ<0,004 respectively). Similar association was found after 12mo FUP. The progression of joint destruction, assessed as the change (Δ) in the number of erosions, joint space narrowings and the total score, was statistically significantly associated with HLA-DRB1∗(SE) genotypes: The carriers of SE (SE+/SE+) double-dose had more advanced progression as compared to (SE+/SE-)/(SE-/SE-) carriers (ρ<0,028, ρ<0,019, ρ<0,035 respectively). Conclusion. Our data suggest that HLA-DRB1 (SE+) gene and TNFα (-308G>A) polymorphisms are associated with the progression of radiographic joint destruction in early, active RA patients managed according to "Treat to target" stratagy.