The Use of Plasmapheresis in Treatment of Patients with Infertility, Peritoneal Endometriosis and Nat2 Gene Polymorphism

It is known that 30–40 % of patients with peritoneal endometriosis suffer from infertility. Half of the patients with endometriosis are identified point mutation in NAT2 – gene, which plays an important role in the acetylation of aromatic and heterocyclic amines, in the accumulation of endotoxins, activation of free radical oxidation, impaired microcirculation. These factors involve the use of methods of gemapheresis which have detoxification, the blood rheology corrective and immune corrective effects. The purpose of this study was to evaluate the efficacy of therapeutic plasma exchange in treatment of patients with peritoneal form of endometriosis, infertility and point mutations in the gene NAT2. The study included 140 patients with infertility, peritoneal form of endometriosis and point mutations in the gene NAT2. All patients are performed laparoscopy, coagulation foci of endometriosis. In the following 93 (66.4 %) patients were treated with a the course of therapeutic plasmapheresis using the apparatus «PCS-2» with the removal of 20–25 % the volume of circulating plasma with replacement plasma of crystalloid and colloid solutions. Before treatment were shown the signs of endotoxemia, activation of oxidative stress. After treatment with the use of plasmapheresis was revealed the significant reduction of endogenous intoxication parameters and oxidative stress. Also is noted the increase in the pregnancy rate, both independently and in IVF programs, especially during the first 3 months after treatment. The findings suggest that the efficiency of the proposed comprehensive treatment techniques (laparoscopy and subsequent course of therapeutic plasmapheresis) of patients with peritoneal endometriosis and infertility and with point mutations in the gene NAT2. The use of plasmapheresis is pathogenetically justified in patients of the studied group

THE USE OF PLASMAPHERESIS IN TREATMENT OF PATIENTS WITH INFERTILITY, PERITONEAL ENDOMETRIOSIS AND NAT2 GENE POLYMORPHISM

It is known that 30–40 % of patients with peritoneal endometriosis suffer from infertility. Half of the patients with endometriosis are identified point mutation in NAT2 – gene, which plays an important role in the acetylation of aromatic and heterocyclic amines, in the accumulation of endotoxins, activation of free radical oxidation, impaired microcirculation. These factors involve the use of methods of gemapheresis which have detoxification, the blood rheology corrective and immune corrective effects.The purpose of this study was to evaluate the efficacy of therapeutic plasma exchange in treatment of patients with peritoneal form of endometriosis, infertility and point mutations in the gene NAT2.The study included 140 patients with infertility, peritoneal form of endometriosis and point mutations in the gene NAT2. All patients are performed laparoscopy, coagulation foci of endometriosis. In the following 93 (66.4 %) patients were treated with a the course of therapeutic plasmapheresis using the apparatus «PCS-2» with the removal of 20–25 % the volume of circulating plasma with replacement plasma of crystalloid and colloid solutions. Before treatment were shown the signs of endotoxemia, activation of oxidative stress. After treatment with the use of plasmapheresis was revealed the significant reduction of endogenous intoxication parameters and oxidative stress. Also is noted the increase in the pregnancy rate, both independently and in IVF programs, especially during the first 3 months after treatment. The findings suggest that the efficiency of the proposed comprehensive treatment techniques (laparoscopy and subsequent course of therapeutic plasmapheresis) of patients with peritoneal endometriosis and infertility and with point mutations in the gene NAT2. The use of plasmapheresis is pathogenetically justified in patients of the studied group

N-acetyltransferase 2 (NAT2) Gene Polymorphisms and the Effectiveness of Infertility Treatment in Patients with Peritoneal Endometriosis

Today, infertility has become a global issue. WHO ranks it the fifth among the major diseases of those below 60 years, after alcoholism, depression, injuries and eyesight disorders. Numerous studies conducted on the problems of infertility in endometriosis still do not offer clear answers regarding the pathogenesis and mechanisms of this disease and its influences on fertility. According to the survey results, point mutations of the NAT2 gene (NAT2*5 and NAT2*6) have been identified in 75.6% of the patients with infertility problems and the peritoneal form of endometriosis, that create “slow” allelic variants, which exceed the average index in the population. The peculiarities of the NAT2 gene polymorphisms have been proven to be associated with the effectiveness of the infertility treatment of female patients with peritoneal endometriosis. In the group of non-pregnant patients, the presence of с.341Т>C, c.481C>T, c.590G>A and c.803A>G heterozygous point mutations are 73.2, 73.2, 5.4, and 62.5%, respectively. The significant difference in the comparison of the allelic polymorphism during the various stages of the endometriosis was not identified. At stage III-IV endometriosis the frequency of three and more point substitutions was significantly higher. NAT2 gene polymorphisms can find use as an additional criterion for predicting the effectiveness of the infertility treatment of patients with peritoneal endometriosis

Інтродукційний потенціал хвойних в мікроландшафтних дендрокомпозиціях Криворізького ботанічного саду НАН України

The aim of the study is to determine main effective microcompositional solutions with using conifers and shrubs in the Cryvyj Rih botanical garden of NAS of Ukraine. The tasks included the study of principles of the construction and taxonomic structure of microlandscape dendrocompositions, evaluation of living states, biomorphological characteristics and decorativeness of each variety and cultivar of coniferous introducents. The objects of the studies were coniferous introducents, used in microlandscape dendrocompositions of the collection fund of CBG. The evaluation of the living state of plants was realized by the methodology of V.T. Yarmishko (2002), decorativeness – T. G. Tamberg and T.N. Ulianova (1969), biomorphological analysis – by I.G. Serebriakov (1962), distribution by the crown form – by A.I. Kolesnikov (1974). There were separated 21 nature dendrocompositions, which taxonomic composition counts 13 varieties, 38 cultivars of 9 geni and 4 families. The main families in these compositions are Сupressaceae and Pinaceae. The Juniperus L. genus is the most widespread – 2 varieties and 14 cultivars. The tree living form is inherent to 28 taxons of conifers, bush – 23 taxons. At creating dendrocompositions, there were used ecological, system and physionomic principles. Our analysis divided them in pure coniferous (14) and mixed coniferous-foliar (7), mono-variant (4) and multi-variant (17) of 2-4 varieties. The age of plants was 15-35 years.Conifers were divided in 7 groups by form: conic (49 %), spread (25 %), column-like (12 %), creeping (6 %), spheric  (4%), weeping (2 %), pillow-like (2%). The following 3 groups wee separated by the needles coloration: green (43%), yellow and yellow-motley (30%), grey-blue (27 %). Among the whole number of studied coniferous plants the high living state level was observed in 80% of units, and decorative one – in 74%. All aforesaid microlandscape dendrocompositions of conifers are perspective for using in gardening of territories of settlements of the steppe zone of Ukraine of different destinationsВ статті наведені результати досліджень еколого-біологічних особливостей хвойних інтродуцентів в мікроландшафтних дендрокомпозиціях різного типу колекційних насаджень Криворізького ботанічного саду НАН України. Встановлена їх перспективність для подальшого використання в озелененні промислових міст степової зони України на основі визначення життєвого стану, біоморфологічних характеристик та декоративност

Programmed Death-1 and Its Ligand Are Novel Immunotolerant Molecules Expressed on Leukemic B Cells in Chronic Lymphocytic Leukemia

Programmed death-1 (PD-1) is an immunoreceptor predominantly expressed on exhausted T cells, which through an interaction with its ligand (PD-L1), controls peripheral tolerance by limiting effector functions of T lymphocytes. qRT-PCR for PD-1, PD-L1 and their splicing forms as well as flow cytometric assessment of surface expression was performed in a cohort of 58 chronic lymphocytic leukemia (CLL) patients. In functional studies, we assessed the influence of the proliferative response of leukemic B-cells induced by IL-4 and CD40L on PD-1 transcripts and expression on the protein level. The median level of PD-1, but not PD-L1, transcripts in CLL patients was higher in comparison to healthy volunteers (HVs, n = 43, p = 0.0057). We confirmed the presence of PD-1 and PD-L1 on the CLL cell surface, and found the expression of PD-1, but not PD-L1, to be higher among CLL patients in comparison to HVs (47.2% vs. 14.8%, p<0.0001). The Kaplan-Meier curves for the time to progression and overall survival in groups with high and low surface expression of PD-1 and PD-L1 revealed no prognostic value in CLL patients. After stimulation with IL-4 and CD40L, protein expression of PD-1 was significantly increased in samples that responded and up-regulated CD38. PD-1, which is aberrantly expressed both at mRNA and cell surface levels in CLL cells might represent a novel immunotolerant molecule involved in the pathomechanism of the disease, and could provide a novel target for future therapies

Chimeric Antigen Receptor Signaling Domains Differentially Regulate Proliferation and Native T Cell Receptor Function in Virus-Specific T Cells

The efficacy of T cells expressing chimeric antigen receptors (CARs) for solid tumors has been limited by insufficient CAR T cell expansion and persistence. The use of virus-specific T cells (VSTs) as carriers for CARs may overcome this limitation since CAR-VSTs can be boosted by viral vaccines or oncolytic viruses. However, there is limited understanding of the optimal combination of endodomains and their influence on the native T cell receptor (TCR) in VSTs. We therefore compared the function of GD2.CARs expressing the TCR zeta chain (ζ) alone or combined with endodomains from CD28 and 4-1BB in varicella zoster virus-specific (VZV) T cells. VZVSTs expressing GD2-CARs recognized VZV-derived peptides and killed GD2-expressing tumor cells. However, after repeated stimulation through their native TCR, the expansion of GD2-CAR.CD28ζ-VZVSTs was 3.3-fold greater (p &lt; 0.001) than non-transduced VZVSTs, whereas GD2-CARζ- and GD2-CAR.41BBζ inhibited VZVST expansion (p &lt; 0.01). Compared to control VZVSTs, GD2-CAR.ζ VZVSTs showed a greater frequency of apoptotic (p &lt; 0.01) T cells, whereas prolonged downregulation of the native αβ TCR was observed in GD2-CAR.41BBζ VZVSTs (p &lt; 0.001). We confirmed that CD28ζ can best maintain TCR function by expressing GD2.CARs in Epstein-Barr virus-specific T cells and CD19-CARs in VZVSTs. In response to CAR stimulation VSTs with CD28ζ endodomains also showed the greatest expansion (6 fold &gt; GD2-CAR.41BBζ VZVSTs (p &lt; 0.001), however anti-tumor efficacy was superior in GD2-CAR.41BBζ-VZVSTs. These findings demonstrate that CAR signaling domains can enhance or diminish the function of the native TCR and indicate that only CD28ζ may preserve the function of the native TCR in tonically signaling CAR-VSTs

The Eurasian Modern Pollen Database (EMPD), version 2

The Eurasian (née European) Modern Pollen Database (EMPD) was established in 2013 to provide a public database of high-quality modern pollen surface samples to help support studies of past climate, land cover, and land use using fossil pollen. The EMPD is part of, and complementary to, the European Pollen Database (EPD) which contains data on fossil pollen found in Late Quaternary sedimentary archives throughout the Eurasian region. The EPD is in turn part of the rapidly growing Neotoma database, which is now the primary home for global palaeoecological data. This paper describes version 2 of the EMPD in which the number of samples held in the database has been increased by 60 % from 4826 to 8134. Much of the improvement in data coverage has come from northern Asia, and the database has consequently been renamed the Eurasian Modern Pollen Database to reflect this geographical enlargement. The EMPD can be viewed online using a dedicated map-based viewer at https://empd2.github.io and downloaded in a variety of file formats at https://doi.pangaea.de/10.1594/PANGAEA.909130 (Chevalier et al., 2019)Swiss National Science Foundation | Ref. 200021_16959

The Eurasian Modern Pollen Database (EMPD), version 2

The Eurasian (nee European) Modern Pollen Database (EMPD) was established in 2013 to provide a public database of high-quality modern pollen surface samples to help support studies of past climate, land cover, and land use using fossil pollen. The EMPD is part of, and complementary to, the European Pollen Database (EPD) which contains data on fossil pollen found in Late Quaternary sedimentary archives throughout the Eurasian region. The EPD is in turn part of the rapidly growing Neotoma database, which is now the primary home for global palaeoecological data. This paper describes version 2 of the EMPD in which the number of samples held in the database has been increased by 60% from 4826 to 8134. Much of the improvement in data coverage has come from northern Asia, and the database has consequently been renamed the Eurasian Modern Pollen Database to reflect this geographical enlargement. The EMPD can be viewed online using a dedicated map-based viewer at https://empd2.github.io and downloaded in a variety of file formats at https://doi.pangaea.de/10.1594/PANGAEA.909130 (Chevalier et al., 2019).Peer reviewe