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Cytokine profile features in women with reproductive disorders exposed to excessive environmental contamination with hydroxybenzene 暴露于过量环境污染的羟基苯的生殖障碍妇女的细胞因子特征
Pub Date : 2021-03-01 DOI: 10.15789/1563-0625-CPF-2054
O. Kazakova, O. Dolgikh
Excessive activity of cytokines, as well as their deficiency, promote a regulatory imbalance of immune system, which may cause persistent inflammation and, as a consequence, loss of pregnancy. The purpose of our work was to study the role of cytokine expression in the development of endometriosis in women exposed to excessive environmental contamination with hydroxybenzene. The study involved 106 women of reproductive age, divided into 4 groups according to two criteria: the presence or absence of reproductive disorders (endometriosis), as well as levels of blood contamination with hydroxybenzene compared to the reference ranges. The groups of women were comparable in age, ethnicity, and social status. The level of phenol in blood was measured by gas chromatography, and the cytokine levels were determined by enzyme immunoassay. The use of parametric and nonparametric statistical criteria as well as adjustments for multiple Bonferoni comparisons, allowed us to establish significant differences between the groups, according to the levels of IL-1β, IL-8, IL-10. The expression of interleukin 8 (IL-8) in women with endometriosis was found to be significantly higher than in healthy ones. At the same time, the observed features of IL-8, interleukin 1β (IL-1β) expression correlate with the overproduction of interleukin 10 (IL-10) associated with excessive contamination of bio-environments with hydroxybenzene. The results of using non-parametric correlation analysis of the Spearman data revealed a positive correlation between IL-10 production and hydroxybenzene levels in the blood, as well as inverse relationship between IL-10 and IL-8 expression. Thus, evidence has been obtained of the involvement of exogenous estrogen hydroxybenzene in development of reproductive disorders, probably, formed under active participation of increased anti-inflammatory IL-10 cytokine, which, by antagonism to proinflammatory mediators (e.g., IL-8), seems to promote apparent transition from acute phase of endometriosis to chronic disorder, thus reducing the reproductive potential of women. It is known that IL-8 expression significantly correlates with development of endometriosis, but excessive phenol exposure may increase the anti-inflammatory IL-10 expression, thereby suppressing the activity of IL-8. Suppressed activity of proinflammatory cytokines by phenol may lead to chronic inflammation and impaired reproductive functions.
细胞因子的过度活性及其缺乏会促进免疫系统的调节失衡,这可能会导致持续的炎症,从而导致流产。我们工作的目的是研究细胞因子表达在暴露于羟基苯过度环境污染的妇女子宫内膜异位症发展中的作用。这项研究涉及106名育龄妇女,根据两个标准分为4组:是否存在生殖障碍(子宫内膜异位症),以及与参考范围相比血液中羟基苯的污染水平。这些妇女群体在年龄、种族和社会地位方面具有可比性。通过气相色谱法测定血液中的苯酚水平,并通过酶免疫测定法测定细胞因子水平。使用参数和非参数统计标准以及对多种Bonferoni比较的调整,使我们能够根据IL-1β、IL-8和IL-10的水平确定各组之间的显著差异。子宫内膜异位症妇女白细胞介素8(IL-8)的表达显著高于健康妇女。同时,观察到的IL-8、白细胞介素1β(IL-1β)表达的特征与白细胞介蛋白10(IL-10)的过度产生相关,白细胞介因子10与羟基苯对生物环境的过度污染有关。Spearman数据的非参数相关分析结果显示,IL-10的产生与血液中的羟基苯水平呈正相关,IL-10与IL-8的表达呈反比。因此,已经获得了外源性雌激素-羟基苯参与生殖疾病发展的证据,可能是在抗炎IL-10细胞因子增加的积极参与下形成的,通过对抗促炎介质(如IL-8),似乎促进了从子宫内膜异位症急性期到慢性疾病的明显转变,从而降低了妇女的生殖潜力。众所周知,IL-8的表达与子宫内膜异位症的发展显著相关,但过量的苯酚暴露可能会增加抗炎IL-10的表达,从而抑制IL-8的活性。苯酚抑制促炎细胞因子的活性可能导致慢性炎症和生殖功能受损。
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引用次数: 0
Influence of metabolites of microorganisms from permafrost on the synthesis cytokines by human peripheral blood mononuclear cells in vitro 冻土微生物代谢物对体外人外周血单核细胞合成细胞因子的影响
Pub Date : 2021-03-01 DOI: 10.15789/1563-0625-IOM-2014
S. Kolyvanova, L. F. Kalenova
Permafrost is a unique ecosystem characterized by consistently negative temperatures. It has been shown that microorganisms can be there in a state of hypometabolism or anabiosis during geological time. It is known that microorganisms occupy a wide habitat due to the presence of multifunctional systems of adaptation and communication. One of the manifestations of these systems is the production of secondary metabolites (MBs), which include signaling molecules that do not have strict species specificity. The biological activity of signaling molecules largely depends on the number of bacterial cells and the temperature of their cultivation.In this work we used secondary MBs of Bacillus sp. from Permafrost obtained at different temperatures of microorganism cultivation (at -5 °C – “cold” MBs and at 37 °C – “warm” MBs) in doses of 0,05 × 106 (small dose) of microbial cells (m.cl.) in ml of saline or 500 × 106 (high dose) m.cl./ml. The influence of MB of Bacillus sp. for the TNFα, IL-1β, IL-8, IL-2, IFNγ, IL-4 and IL-10 production by human peripheral blood mononuclear cells (MNC) in supernatants of 24-hour cell cultures was estimated by ELISA whith using the “VectorBEST” test system (Russia) on a LUCY-2 (ANTHOS) spectrophotometer (Austria).It was found that the activity of synthesis by human MNC of the main spectrum of cytokines significantly increased (p < 0.01 for all indicators) under the influence of MB Bacillus sp. regardless of the temperature of their cultivation and the dose of bacteria. The exception was IL-8, the level of which under the influence of a high dose of “warm” MBs didn’t differ from the control. Compared to PHA the cytokines synthesis by MNC depended on the dose and the temperature of obtaining of MBs. Thus, under the influence of “warm” MBs the level of TNFα was significantly lower than its level under the influence of PHA regardless of the dose. Regardless of the temperature of obtaining metabolites the level of IL-8 under the influence of metabolites from a dose of 500 × 106 m.cl. was reduced relative to the PHA group. Comparison of the influence of “warm” and “cold” MBs of Bacillus sp. showed that small doses of “cold” metabolites to a greater extent stimulate the synthesis of pro-inflammatory cytokines (TNFα, IL-1β, IL-8, IFNγ). High doses of “heat” metabolites of Bacillus sp. to a greater extent they activate human MNCs for the synthesis of anti-inflammatory cytokines (IL- 4 and IL-10). Considering that TNFα, IL-1β and IL-10 are cytokines of systemic action and are responsible not only for the activation of the immune system, but also for the mobilization of other regulatory systems of the organism, it can be assumed that the secondary metabolites of microorganisms from Permafrost will be efficient as a substrate for the development of new immunomodulators and adaptogens in the future.
永久冻土是一个独特的生态系统,其特征是持续的负温度。研究表明,在地质时期,微生物可能处于低代谢或复苏状态。众所周知,由于存在多功能的适应和交流系统,微生物占据了广泛的栖息地。这些系统的表现之一是产生次生代谢物(mb),其中包括没有严格物种特异性的信号分子。信号分子的生物活性在很大程度上取决于细菌细胞的数量和培养温度。在这项工作中,我们使用了在不同微生物培养温度下(-5°C -“冷”mb和37°C -“热”mb)从冻土中获得的芽孢杆菌的次级mb,剂量为0.05 × 106(小剂量)微生物细胞(毫微克/毫升)ml生理盐水或500 × 106(高剂量)毫微克/毫升。采用“VectorBEST”检测系统(俄罗斯)和LUCY-2 (ANTHOS)分光光度计(奥地利),采用酶联免疫吸附法测定Bacillus sp. MB对人外周血单核细胞(MNC) 24小时培养上清中产生TNFα、IL-1β、IL-8、IL-2、IFNγ、IL-4和IL-10的影响。结果表明,无论培养温度和细菌剂量如何,受MB芽孢杆菌的影响,人MNC合成主要谱因子的活性均显著升高(各指标均p < 0.01)。唯一的例外是IL-8,在高剂量“热”mb的影响下,其水平与对照组没有差异。与PHA相比,MNC的细胞因子合成取决于MBs的剂量和获得温度。因此,在“温”mb的影响下,TNFα的水平无论剂量如何都显著低于PHA影响下的水平。无论获得代谢物的温度如何,剂量为500 × 106 m.cl时,代谢物对IL-8水平的影响。相对于PHA组降低。比较芽孢杆菌“温”和“冷”代谢产物的影响表明,小剂量的“冷”代谢产物更大程度上刺激促炎细胞因子(TNFα、IL-1β、IL-8、IFNγ)的合成。高剂量芽孢杆菌的“热”代谢物在更大程度上激活人类MNCs合成抗炎细胞因子(IL- 4和IL-10)。考虑到TNFα, IL-1β和IL-10是全身性的细胞因子,不仅负责免疫系统的激活,而且还负责生物体其他调节系统的动员,可以假设永久冻土微生物的次级代谢产物将有效地作为未来开发新的免疫调节剂和适应原的底物。
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引用次数: 0
Effect of β-alanine on humoral immune response in low-dose allergy model β-丙氨酸对低剂量变态反应模型体液免疫反应的影响
Pub Date : 2021-03-01 DOI: 10.15789/1563-0625-EOB-2008
D. Chudakov, O. Kotsareva, D. S. Tsaregorotseva, E. Kashirina, G. Fattakhova
At the present time, the efforts of many research groups around the world are aimed at finding new factors triggering the allergic sensitization process linked with IgE synthesis to harmless allergens. According to the recent data, production of tissue cytokines is induced in tissue cells by alarmins, thus, in turn, eliciting pro-allergic immune response. Previously we have shown that β-alanine could be a potential alarmin capable to stimulate production of tissue cytokines. The aim of this work was to determine the impact of β-alanine on humoral immune response in low-dose allergy model. BALB/c mice were immunized by recombinant Asp f 2 protein or commercial ovalbumin (OVA) in the withers 3 times a week with or without β-alanine supplementation. To determine the mechanism of β-alanine effect, α-L-alanine, an isomer which is not MrgD receptor ligand, and β-aminoisobutyrate with β-alanine-like affinity to MrgD ligand, were compared. According to our data, β-alanine stimulated specific IgE and IgG1 production in a short-term course (7 immunizations) and enhanced antibody affinity after long-term (14 immunizations) protocol in the case of low-immunogenic protein Asp f 2. In the case of high-immunogenic OVA protein, the impact of β-alanine was significant only upon antibody affinity. Hence, β-alanine accelerates specific IgE production in the case of low-immunogenic protein. The impact of β-alanine on specific IgE production was not linked to specific MrgD receptor activation, because β-aminoisobutyrate, which is the other ligand of this receptor, did not have a similar effect upon humoral immune response. The effect of β-alanine on IgG1 production seems also independent of MrgD receptor, since the common proteinogenic amino acid α-L-alanine also enhanced specific IgG1 production. The effect of β-alanine on humoral immune response could be linked to its non-specific action, e.g., due to its ability to induce oxidative stress through blocking taurine transporter, or due to its ability to stimulate cellular metabolism.
目前,世界各地许多研究小组的努力旨在寻找与IgE合成相关的过敏致敏过程的新因素,以对抗无害的过敏原。根据最近的数据,危言耸听在组织细胞中诱导组织细胞因子的产生,从而引发促过敏免疫反应。以前我们已经证明,β-丙氨酸可能是一种潜在的危言耸听蛋白,能够刺激组织细胞因子的产生。本工作的目的是确定β-丙氨酸对低剂量变态反应模型中体液免疫反应的影响。用重组Asp f2蛋白或商品卵清蛋白(OVA)免疫BALB/c小鼠,每周3次,添加或不添加β-丙氨酸。为了确定β-丙氨酸效应的机制,比较了非MrgD受体配体的异构体α-L-丙氨酸和对MrgD配体具有β-丙氨酸样亲和力的β-氨基异丁酸。根据我们的数据,在低免疫原性蛋白Asp f 2的情况下,β-丙氨酸在短期内(7次免疫)刺激特异性IgE和IgG1的产生,并在长期(14次免疫)方案后增强抗体亲和力。在高免疫原性OVA蛋白的情况下,β-丙氨酸的影响仅对抗体亲和力显著。因此,在低免疫原性蛋白质的情况下,β-丙氨酸加速特异性IgE的产生。β-丙氨酸对特异性IgE产生的影响与特异性MrgD受体的激活无关,因为该受体的另一个配体β-氨基异丁酸对体液免疫反应没有类似的影响。β-丙氨酸对IgG1产生的影响似乎也与MrgD受体无关,因为常见的蛋白质生成氨基酸α-L-丙氨酸也增强了特异性IgG1的产生。β-丙氨酸对体液免疫反应的影响可能与其非特异性作用有关,例如,由于其通过阻断牛磺酸转运蛋白诱导氧化应激的能力,或由于其刺激细胞代谢的能力。
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引用次数: 0
Сlinical case of focal alopecia in a child with atopy 特应性儿童局灶性脱发临床病例
Pub Date : 2021-03-01 DOI: 10.15789/1563-0625-CCO-2074
A. A. Barilo, S. Smirnova, I. M. Olyanina
Alopecia areata is a common inflammatory immune-mediated disorder in which autoimmune response is triggered against hair follicles, thus leading to non-scarring hair loss on the scalp, face and other parts of the skin. Despite numerous studies concerning this issue, today there is no consensus on the etiology and pathogenesis of focal alopecia. In the literature, special attention is paid to association of focal alopecia with autoimmune diseases, such as rheumatoid arthritis, celiac disease, type 1 diabetes, psoriasis, autoimmune thyroiditis, vitiligo. Recent studies have identified the association of focal alopecia with atopic diseases (allergic rhinitis, bronchial asthma, atopic dermatitis) and the early debut of severe forms of hair loss. The aim of this study was to present a clinical case of focal alopecia in an 8-year-old girl with atopic bronchial asthma and seasonal allergic rhinitis. As based on detection of eosinophilia in peripheral blood and a high concentration of total IgE in serum, one may assume that atopic alopecia is the cause of focal hair losses in a child with atopy. The patient underwent skin prick testing, in order to determine sensitization for food components, pollen and fungal allergens. As a result of skin testing, a hyperergic reaction (> 15 mm in diameter) to tree pollen was revealed, a positive response (6-9 mm) to oatmeal, a weakly positive reaction (3-5 mm) to whole chicken egg, carrots, tomato, apple, pear, pollen of meadow, cereal, weed grasses was also revealed. With regard of these allergological data, an individual diet was recommended with the elimination of causally significant allergens (including those eliciting weakly positive reactions), external treatment, i.e., topical calcineurin inhibitors administered for 1 month. One month later, an improvement of the pathological process was registered, and 6 months from the start of therapy, complete restoration of hair follicles was noted in the focus of alopecia. The patient was monitored for a year, no complaints of hair loss were noted. The positive effect of elimination against the background of the appropriate elimination diet with respect to causally significant allergens, was also noted when treating her for respiratory allergy, i.e., the patient did not have seasonal manifestations of hay fever over the next pollination period. This clinical case is demonstrated in order to draw special attention of dermatologists, allergologists, immunologists, general practitioners to the issues of focal alopecia in children against the background of typical allergic diseases.
斑秃是一种常见的炎症性免疫介导的疾病,在这种疾病中,自身免疫反应会触发毛囊,从而导致头皮、面部和皮肤其他部位的无疤痕性脱发。尽管有许多关于这一问题的研究,但目前对局灶性脱发的病因和发病机制尚未达成共识。在文献中,特别关注局灶性脱发与自身免疫性疾病的关联,如类风湿关节炎、乳糜泻、1型糖尿病、牛皮癣、自身免疫性甲状腺炎、白癜风。最近的研究已经确定局灶性脱发与特应性疾病(变应性鼻炎、支气管哮喘、特应性皮炎)和早期出现的严重形式的脱发有关。本研究的目的是提出一个临床病例局灶性脱发的8岁女孩特应性支气管哮喘和季节性变应性鼻炎。根据外周血嗜酸性粒细胞的检测和血清中总IgE的高浓度,人们可以假设特应性脱发是特应性儿童局灶性脱发的原因。患者接受皮肤点刺试验,以确定对食物成分、花粉和真菌过敏原的致敏性。皮试结果显示,对树木花粉有超敏反应(直径约15 mm),对燕麦片有正敏反应(6 ~ 9 mm),对全鸡蛋、胡萝卜、番茄、苹果、梨、草甸、谷类、杂草花粉有弱正敏反应(3 ~ 5 mm)。根据这些过敏学数据,建议患者单独饮食,同时消除引起显著过敏性反应的过敏原(包括那些引起弱阳性反应的过敏原),外用治疗,即局部使用钙调磷酸酶抑制剂1个月。1个月后,病理过程有所改善,治疗开始后6个月,脱发焦点处毛囊完全恢复。患者接受了一年的监测,没有发现脱发的症状。在对她进行呼吸道过敏治疗时,也注意到在适当消除饮食的背景下,消除对因果关系显著的过敏原的积极作用,即,在下一个授粉期,患者没有季节性的花粉热表现。这个临床病例是为了引起皮肤科医生,过敏症专家,免疫学家,全科医生对儿童局灶性脱发问题的特别关注,以典型的过敏性疾病为背景。
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引用次数: 1
Changes in the expression of HLA-DR on lymphocyte subpopulations of spouses having children with sporadic congenital heart defects without chromosomal diseases, under the influence of female’s autoserum 女性自身血清影响下散发性先天性心脏缺陷配偶淋巴细胞亚群HLA-DR表达的变化
Pub Date : 2021-03-01 DOI: 10.15789/1563-0625-CIT-2013
A. Shabaldin, S. V. Grivtsova, N. S. Deeva, S. Shmulevich, A. Tsepokina, A. A. Anikeenko, E. Shabaldina, G. Vavin
This study is aimed to investigate the effect of female autoserum on the HLA-DR expression in various subpopulations of lymphocytes obtained from spouses with children with sporadic congenital heart defects without chromosomal diseases. 78 married couples with children with congenital heart disease were included in the study group. The control group was formed from 35 married couples with healthy children. The immune response in a mixed culture of lymphocytes of spouses was evaluated by an increased HLA-DR expression in a mixed culture in relation to spontaneous cultures of lymphocytes. Primary staining of female and male lymphocytes by monoclonal antibodies to CD45 conjugated with various fluorescent dyes (PC-5 and PC-7) was performed to assess the immune response of female lymphocytes to male ones and vice versa. The activating effect of female autoserum on all subpopulations of female lymphocytes simultaneously occurred significantly less frequently in the study group compared to the control. The control group was characterized by the domination of the positive effect of female autoserum on HLA-DR expression for all subpopulations of female lymphocyte. For all female lymphocytes having HLA-DR molecule on its membrane, the blocking effect of female autoserum in the study group was significantly more expressed in relation to the control group. Thus, the effect of female autoserum is manifested in relation to the HLA-DR expression on its own lymphocytes, but not on the lymphocytes of the spouse.
本研究旨在研究女性自体血清对从有散发性先天性心脏缺陷但无染色体疾病的配偶获得的各种淋巴细胞亚群中HLA-DR表达的影响。78对有先天性心脏病子女的已婚夫妇被纳入研究组。对照组由35对有健康子女的已婚夫妇组成。配偶淋巴细胞混合培养中的免疫反应通过混合培养中HLA-DR表达相对于淋巴细胞自发培养的增加来评估。通过与各种荧光染料(PC-5和PC-7)偶联的CD45单克隆抗体对雌性和雄性淋巴细胞进行一次染色,以评估雌性淋巴细胞对雄性淋巴细胞的免疫反应,反之亦然。与对照组相比,研究组女性自体血清对女性淋巴细胞所有亚群的激活作用同时发生的频率显著降低。对照组的特征是女性自体血清对女性淋巴细胞所有亚群的HLA-DR表达的阳性作用占主导地位。对于所有在其膜上具有HLA-DR分子的女性淋巴细胞,与对照组相比,研究组中女性自体血清的阻断作用显著更多地表达。因此,女性自体血清的作用与自身淋巴细胞上的HLA-DR表达有关,而与配偶的淋巴细胞无关。
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引用次数: 0
AB0-incompatibility of mother and fetus: the role of anti-glycan alloantibodies in the hemolytic disease of newborns ab0母婴不相容:抗糖异体抗体在新生儿溶血性疾病中的作用
Pub Date : 2021-03-01 DOI: 10.15789/1563-0625-AOM-1977
P. Obukhova, A. Kachanov, N. Pozdnyakova, M. M. Ziganshina
The mother and fetus incompatibility due to Rh-factor, blood group or other blood factors can lead to hemolytic disease of the fetus and newborn (HDN). HDN is a clinical disease condition of the fetus and newborn as a result of hemolysis, when maternal IgG alloantibodies cross the placenta and destroy the red blood cells of the fetus and newborn. The child disease begins in utero and can dramatically increase immediately after birth. As a result, hyperbilirubinemia and anemia develop, that can lead to abortions, serious complications, or death of the neonates in the absence of proper therapy. The range of HDN has changed significantly now compared to previous decades. Half a century ago, HDN was considered an almost complete synonym of RhD-alloimmunization, and this was a frequent problem for newborns. By now due to the high effective of Rh-conflict prevention, immunological AB0-conflicts have become the most common cause of HDN. The review aimes to one of the main causes of jaundice and anemia in neonates at present, i.e. HDN due to immunological AB0-conflict of mother and newborn (AB0-HDN). The main participants of the AВ0- incompatibility mother and child are considered, namely A- and B-glycans, as well as the corresponding anti-glycan alloantibodies. Close attention is paid to the structure features of glycan alloantigens on the red blood cells of the fetus and adult. The possible correlation of the frequency and severity of HDN with the blood group of mother and child, as well as with the titer of maternal alloantibodies, has been considered. The influence of immunoglobulin G subclasses on the AB0-HDN development has been evaluated. In most cases, AB0-HDN appear when the mother has the blood group 0, and the fetus has the group A (subgroup A1) or the group B. Other rare incidences of AB0-incompatibility with severe course are occurred. As a whole the etiology of AB0-HDN is complex and the HDN severity is influenced by many factors. The authors have analyzed statistical data, as well as the prevalence of AB0-incompatibility and AB0-HDN in various regions of the world. Current approaches to the diagnosis of AB0-HDN are discussed in addition. By now the problems of AB0- HDN occurrence and developing of ways to overcome this disease remain relevant.
由于rh因子、血型或其他血液因素导致的母胎不相容可导致胎儿和新生儿溶血病(HDN)。HDN是一种由溶血引起的胎儿和新生儿的临床疾病,母体的IgG同种异体抗体穿过胎盘,破坏胎儿和新生儿的红细胞。这种儿童疾病始于子宫内,并可能在出生后立即急剧增加。结果,高胆红素血症和贫血的发展,这可能导致流产,严重的并发症,或死亡的新生儿在没有适当的治疗。与过去几十年相比,HDN的范围发生了显著变化。半个世纪以前,HDN几乎被认为是rhd异体免疫的同义词,这是新生儿经常遇到的问题。目前由于rh冲突预防的高效性,免疫性ab0冲突已成为HDN最常见的病因。本文综述了目前引起新生儿黄疸和贫血的主要原因之一,即母亲与新生儿免疫ab0冲突引起的HDN (AB0-HDN)。考虑AВ0-不相容母亲和儿童的主要参与者,即A-和b -聚糖,以及相应的抗聚糖同种抗体。胎儿和成人红细胞上的糖聚糖异体抗原的结构特征引起了人们的密切关注。HDN的发生频率和严重程度可能与母亲和孩子的血型以及母亲的同种异体抗体滴度有关。免疫球蛋白G亚类对AB0-HDN发展的影响已被评估。在大多数情况下,AB0-HDN出现在母亲为0型血,胎儿为A型(A1亚群)或b型血的情况下。总的来说,AB0-HDN的病因复杂,HDN的严重程度受多种因素的影响。作者分析了统计数据,以及ab0 -不相容和AB0-HDN在世界不同地区的流行情况。此外,还讨论了目前AB0-HDN的诊断方法。到目前为止,AB0- HDN发生的问题和克服这种疾病的方法的发展仍然具有重要意义。
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引用次数: 0
Enzymatic characterization of blood lymphocytes in various clinical and pathogenetic variants of respiratory allergy 血液淋巴细胞在呼吸道过敏的各种临床和致病变异中的酶学特征
Pub Date : 2021-03-01 DOI: 10.15789/1563-0625-ECO-2120
A. Lazareva, O. Kolenchukova, S. Smirnova
Allergy is a sufficient social and economic issue of modern times. Altered immunity in allergic disorders is based, mainly, on the lymphocyte disturbances.Immune characteristics depend both on populations and subpopulational profile of immune cells, and on intrinsic intensity and specific features of theirintracellular metabolism. Interest to studies of intracellular metabolism of lymphocytes id determined by high-scale energetic and plastic processes aimed for support of immune homeostasis. The aim of this study was to evaluate the state of intracellular metabolism in peripheral blood lymphocytes from the patients with respiratory allergies of different genesis and respiratory affection.The study included patients with various clinical variants of respiratory allergy (n = 152) at the age of 21 to 63 years old, and virtually healthy blood donors (n = 209), comparable for age and sex. Within these cohorts, we have separately analyzed, e.g., respiratory atopy (atopic rhinosinusitis and atopic bronchial asthma), as well as respiratory pseudoatopy (polypous rhinosinusitis and asthmatic triad). Allergic disorders of upper respiratory ways were diagnosed in a complex clinical examination by allergologist/immunologist and otorhinolaryngologists. Bronchial asthma verification was based on current GINA criteria (2014). We used m standard common clinical methods and specific allergological diagnostics, e.g., allergological anamnesis, skin prick tests, with different non-infectious allergens, measurement of total and specific IgE’s with ELISA method. The parameters of intracellular metabolism of peripheral blood lymphocytes were determined with bioluminescent technique with bacterial luciferase. Actifity of NAD(P) and NAD(P)H enzymes was measured.Dehydrogenase activities in lymphocytes were expressed as enzyme un its (EU, 1 unit = 1 mcmol/min) per 104 cells.Certain changes of intracellular activities in peripheral lymphocytes are revealed, dependent on genesis and origin of allergic inflammation, and affection level of respiratory ways. In respiratory atopy (atopic rhinosinusitis and atopic bronchial asthma), irrelevant on the level of respiratory affection, the activities of intracellular enzymes suggest increased plastic processes that are maximally pronounced in atopic bronchial asthma. In respiratory pseudoatopy (polypous rhinosinusitis and asthmatic triad) the metabolic changes of lymphocytes presume activation of both plastic and energetic processes, with decreased intensity in asthmatic triad condition. Independent on genesis of respiratory allergic inflammation, we have determined low activity of NAD(P)-dependent glutamate dehydrogenase, and NAD(H)-dependent lactate dehydrogenase in allergic inflammation of upper respiratory ways (atopic rhinosinusitis and polypous). Its activity is statistically higher in bronchial asthma (atopic bronchial asthma and asthmatic triad.
过敏是一个充分的社会和经济问题的现代。过敏性疾病的免疫改变主要是基于淋巴细胞紊乱。免疫特性既取决于免疫细胞的群体和亚群特征,也取决于其细胞内代谢的内在强度和特定特征。对淋巴细胞细胞内代谢的研究兴趣是由旨在支持免疫稳态的大规模能量和可塑性过程决定的。本研究的目的是评估不同病因和呼吸道影响的呼吸道过敏患者外周血淋巴细胞的细胞内代谢状态。该研究包括21至63岁的各种呼吸道过敏临床变异患者(n=152),以及在年龄和性别上具有可比性的几乎健康的献血者(n=209)。在这些队列中,我们分别分析了呼吸性特应性(特应性鼻窦炎和特应性支气管哮喘),以及呼吸性假性特应性疾病(息肉性鼻窦炎和哮喘三联征)。过敏学家/免疫学家和耳鼻喉科医生在复杂的临床检查中诊断出上呼吸道过敏性疾病。支气管哮喘验证基于当前的GINA标准(2014)。我们使用了标准的常见临床方法和特定的过敏性诊断方法,如过敏性记忆、皮肤点刺试验、不同的非传染性过敏原、ELISA法测量总IgE和特异性IgE。用细菌萤光素酶生物发光技术测定外周血淋巴细胞的细胞内代谢参数。测定NAD(P)和NAD(P)H酶的活性。淋巴细胞中的脱氢酶活性表示为每104个细胞中的酶un-its(EU,1单位=1mcmol/min)。揭示了外周淋巴细胞细胞内活性的某些变化,这取决于过敏性炎症的发生和起源,以及呼吸方式的影响程度。在呼吸性特应性疾病(特应性鼻窦炎和特应性支气管哮喘)中,与呼吸影响水平无关,细胞内酶的活性表明可塑性过程增加,在特应性哮喘中最为明显。在呼吸性假性特应性(息肉性鼻窦炎和哮喘三联征)中,淋巴细胞的代谢变化假定可塑性和能量过程的激活,哮喘三联征的强度降低。与呼吸道过敏性炎症的发生无关,我们已经确定了NAD(P)依赖性谷氨酸脱氢酶和NAD(H)依赖性乳酸脱氢酶在上呼吸道过敏性炎(特应性鼻窦炎和息肉)中的低活性。其活性在支气管哮喘(特应性支气管哮喘和哮喘三联征)中具有统计学意义。
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引用次数: 0
Polyunsaturated fatty acid status of leukocyte membranes in COPD patients COPD患者白细胞膜的多不饱和脂肪酸状态
Pub Date : 2021-03-01 DOI: 10.15789/1563-0625-PFA-1980
Y. Denisenko, T. Novgorodtseva, V. Knyshova, M. Antonyuk
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引用次数: 1
Gustometry in various variants of bronchial asthma: Sensitivity thresholds for bitter and sweet tast 支气管哮喘各种变异型的味觉测定:苦味和甜味的敏感阈值
Pub Date : 2021-03-01 DOI: 10.15789/1563-0625-GIV-2070
V. Mineev, M. Nyoma, L. Sorokina, P. V. Bryukhanova, D. E. Koksharova
The first studies were published on the possible pathogenetic role of so-called ectopically localized taste receptors in bronchial asthma. The receptors for bitter and sweet taste, may, apparently, have opposite functions, but in available literature there is no data on the balance of sensitivity for bitter and sweet tastes in the same patients with bronchial asthma. The aim of the present work is to simultaneously assess the sensitivity of canonical lingual receptors to bitter and sweet taste in the same patients with different clinical variants of bronchial asthma by methods applicable in wide clinical practice. 16 healthy persons and 35 patients with bronchial asthma were examined at the M.V. Chernorutsky Clinics of Hospital Therapy at First St. Petersburg State I. Pavlov Medical University. The sensitivity for bitter taste was assessed using The Frey Scientific 569885 PTC Taste Paper test strip kit containing phenylthiourea solution. Sucrose solutions at concentrations of 0.3; 0,4; 0,5; 0,6; 0,7; 0,8; 0,9 % for determination of individual value of taste thresholds to sweet taste were used. The bitter-to-sweet taste sensitivity balance was assessed on the basis of an original “bitter/sweet taste sensitivity” index. The highest values of index of bitter/sweet taste was found in the allergic variant of bronchial asthma: its values are significantly different from those in healthy persons only at low sucrose concentrations (0.3-0.4%). The factor analysis revealed an association between taste imbalance (a shift towards high sensitivity to sweet taste) and key characteristics of bronchial asthma, including severity of bronchial asthma course, duration of inhaled glucocorticosteroid use and inefficiency of β2-agonists use at pre-clinical stage. It has been revealed by gustometry that in the allergic variant of bronchial asthma there is a decreased sensitivity for bitter test substance (phenylthiourea), along with higher sensitivity for sweet taste (sucrose).
关于所谓的异位味觉受体在支气管哮喘中可能的致病作用的第一项研究发表了。苦味和甜味的受体显然可能具有相反的功能,但在现有文献中,没有关于支气管哮喘患者对苦味和甜味敏感度平衡的数据。本工作的目的是通过适用于广泛临床实践的方法,同时评估具有不同临床变异的支气管哮喘患者的典型舌受体对苦味和甜味的敏感性。16名健康人和35名支气管哮喘患者在圣彼得堡第一国立巴甫洛夫医科大学的M.V.Chernorutsky医院治疗诊所接受了检查。使用含有苯基硫脲溶液的Frey Scientific 569885 PTC taste Paper测试条试剂盒评估苦味的敏感性。浓度为0.3的蔗糖溶液;0.4;0.5;0.6;0.7;0.8;使用0.9%来测定甜味的味觉阈值的个体值。根据原始的“苦味/甜味敏感性”指数评估苦味与甜味的敏感性平衡。苦味/甜味指数的最高值出现在支气管哮喘的过敏性变体中:其值仅在低蔗糖浓度(0.3-0.4%)下与健康人的值有显著差异。因子分析揭示了味觉失衡(向甜味高度敏感的转变)与支气管哮喘的关键特征之间的关联,包括支气管哮喘病程的严重程度、吸入性糖皮质激素使用的持续时间以及临床前阶段β2-激动剂使用的低效率。味觉测定法显示,在支气管哮喘的过敏性变体中,对苦味测试物质(苯基硫脲)的敏感性降低,对甜味(蔗糖)的敏感性升高。
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引用次数: 0
Common variable immunodeficiency disorder: a clinical case 常见可变免疫缺陷综合征1例临床分析
Pub Date : 2021-03-01 DOI: 10.15789/1563-0625-CVI-2089
E. Sobko, I. Demko, I. Soloveva, A. Kraposhina, N. Gordeeva, D. Anikin, N. Pronkina, O. Ischenko
Primary immunodeficiency is a rare congenital pathology associated with failure of immune system, manifested by disturbances of its functions. These defects lead to increased susceptibility of patients to various infectious agents, as well as the development of autoimmune, malignant and other diseases. Primary immunodeficiency is classified as a rare disease, which was previously associated with a poor prognosis with a high risk of mortality in childhood. To date, the emergence of highly effective treatment methods has changed the course and prognosis of these diseases. Clinicians of various specialties increasingly meet with this pathology in everyday practice, including adult age cohorts. In this regard, early diagnosis of primary immunodeficiency in adults becomes relevant, being associated with choosing optimal therapy, prevention of severe internal organ damage, determination of management strategy for the patient, as well as the need to identify inherited disorders and provide information to the patient’s family. Delayed verification of the diagnosis may cause disability of the patient and development of irreversible, often fatal complications. This article presents our own clinical case with a newly diagnosed clinical condition: Common variable immunodeficiency disorder (CVID), the most common form of primary immunodeficiency in adults. The symptoms of common variable immunodeficiency disorder appear in these patients in adulthood, but a high-quality collected history of the disease will allow you to trace symptoms in the patients even since early childhood. There is a common gap for several years between the onset of the disease and clinical diagnosis, since erroneous diagnosis is often made due to non-specific clinical symptoms that resemble other, more frequent diseases. The prognosis of patients with CVID depends on several factors: frequency of infections, structural disorders in the lungs, the occurrence of autoimmune diseases and the success of infection prevention. Thus, a variety of clinical forms of primary immunodeficiency, lack of awareness of doctors about this pathology, complexity of immunological examination in the general medical network lead to the fact that CVID is not diagnosed for long terms, and patients do not receive the necessary pathogenetic therapy. There is a need for drawing attention of doctors of various disciplines to the fact that the recurrent inflammatory processes of various localization, which are difficult to respond to adequate traditional therapy, may be caused by changes in the immune system, including congenital, genetically determined immunodeficiency.
原发性免疫缺陷是一种罕见的与免疫系统衰竭相关的先天性病理,表现为免疫系统功能紊乱。这些缺陷导致患者对各种传染源的易感性增加,以及自身免疫性、恶性和其他疾病的发展。原发性免疫缺陷被归类为一种罕见疾病,以前与儿童期预后不良和高死亡率有关。迄今为止,高效治疗方法的出现改变了这些疾病的病程和预后。不同专业的临床医生在日常实践中越来越多地遇到这种病理学,包括成年患者。在这方面,成人原发性免疫缺陷的早期诊断变得重要,这与选择最佳治疗、预防严重的内部器官损伤、确定患者的管理策略以及确定遗传性疾病和向患者家属提供信息的必要性有关。诊断的延迟验证可能会导致患者残疾,并发展成不可逆转的、往往是致命的并发症。这篇文章介绍了我们自己的一个新诊断的临床情况:常见的可变免疫缺陷障碍(CVID),成人最常见的原发性免疫缺陷。这些患者成年后会出现常见的可变免疫缺陷疾病的症状,但高质量的病史收集将使您能够追踪患者的症状,即使是从儿童早期开始。该疾病的发病和临床诊断之间存在几年的共同差距,因为错误诊断往往是由于类似于其他更常见疾病的非特异性临床症状造成的。CVID患者的预后取决于几个因素:感染频率、肺部结构紊乱、自身免疫性疾病的发生和感染预防的成功。因此,原发性免疫缺陷的多种临床形式,医生对这种病理缺乏认识,普通医疗网络中免疫检查的复杂性,导致CVID长期得不到诊断,患者得不到必要的病因治疗。需要提请各个学科的医生注意这样一个事实,即各种定位的复发性炎症过程可能是由免疫系统的变化引起的,包括先天性、遗传性免疫缺陷。
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引用次数: 0
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Medical immunology (London, England)
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