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The impact of adjuvanted and non-adjuvanted influenza vaccines on in vitro lymphocyte immunophenotype 佐剂和非佐剂流感疫苗对体外淋巴细胞免疫表型的影响
Pub Date : 2023-08-06 DOI: 10.15789/2220-7619-tio-1250
E. Khromova, N. Akhmatova, M. Kostinov, S. Skhodova, V. Stolpnikova, A. Vlasenko, V. Polishchuk, A. Shmitko
Vaccination is the most effective method of influenza prophylaxis resulting in reduced frequency and severity of complications. Currently, for the prevention of influenza, inactivated split and subunit vaccines as the safest and promoting formation of protective level of strain-specific virus neutralizing antibodies are used. It is known that not all inactivated vaccines are effective enough for select human groups. While nowadays the level of public health is low, there is a need to improve the effectiveness of vaccines that should activate all chains of the immune system. In order to enhance intensity of influenza virus strain-specific antibody production, adjuvant vaccines exerting other mechanisms to activate humoral and cellular immunity compared to non-adjuvant vaccines have been used. The aim of the study was to examine lymphocyte immunophenotype in 27 healthy donors treated with polymer-subunit (immunoadjuvant) and non-adjuvanted split and subunit influenza vaccines. Materials and methods. Peripheral blood lymphocyte subpopulations were studied in vitro by flow cytometer FC-500 Cytomics (Beckman Coulter, USA) using FITC- and PE-labeled monoclonal antibodies (mAbs). Results. All examined influenza vaccines activate the effectors of cellular immunity, increasing the number of NK-cells (CD16/56), NKT-lymphocytes (CD3/CD16/56), B-lymphocytes (CD45/CD20), activated (CD3/HLA-DR) and cytotoxic (CD8/HLA-DR) T-lymphocytes, as well as cells bearing early activation marker (CD45/CD25). Among them the immunoadjuvant vaccine showed the greatest potential to induce cellular response eliciting regulatory mechanisms that prevent hyperactivation, stimulating growth of NK (CD16/56), NKT-cells (CD3/CD16/56), B-lymphocytes (CD45/CD20), activated (CD3/HLA-DR) and cytotoxic (CD8/HLA-DR) T-lymphocytes, T-regulatory cells (Tregs, CD4/CD25/Foxp3). Conclusion. Vaccination against influenza besides the formation of specific antibodies render a transient, immunomodulating effect that is more noticeable after immunoadjuvant vaccine. It can be assumed that vaccination of people with dysfunctions of the immune system an additional prophylactic effect will be observed.
疫苗接种是预防流感最有效的方法,可减少并发症的发生频率和严重程度。目前,预防流感使用的是最安全的灭活分裂疫苗和亚单位疫苗,可促进形成具有保护水平的毒株特异性病毒中和抗体。众所周知,并非所有灭活疫苗对特定人群都足够有效。虽然目前公共卫生水平较低,但有必要提高疫苗的有效性,以激活免疫系统的所有链。为了增强流感病毒株特异性抗体的产生强度,与非佐剂疫苗相比,佐剂疫苗发挥了其他机制来激活体液和细胞免疫。本研究的目的是检测27名健康供体接受聚合亚单位(免疫佐剂)和非佐剂分裂和亚单位流感疫苗治疗的淋巴细胞免疫表型。材料和方法。体外外周血淋巴细胞亚群研究采用流式细胞仪FC-500 Cytomics (Beckman Coulter, USA),使用FITC和pe标记的单克隆抗体(mab)。结果。所有检测到的流感疫苗都能激活细胞免疫效应,增加nk细胞(CD16/56)、nkt淋巴细胞(CD3/CD16/56)、b淋巴细胞(CD45/CD20)、活化(CD3/HLA-DR)和细胞毒性(CD8/HLA-DR) t淋巴细胞的数量,以及携带早期活化标记(CD45/CD25)的细胞的数量。其中,免疫佐剂疫苗显示出最大的诱导细胞反应的潜力,诱导调节机制,防止过度活化,刺激NK (CD16/56), nkt细胞(CD3/CD16/56), b淋巴细胞(CD45/CD20),活化(CD3/HLA-DR)和细胞毒性(CD8/HLA-DR) t淋巴细胞,t调节细胞(Tregs, CD4/CD25/Foxp3)的生长。结论。除了形成特异性抗体外,接种流感疫苗还能产生短暂的免疫调节作用,这种作用在接种免疫佐剂疫苗后更为明显。可以假设,免疫系统功能障碍的人接种疫苗,将观察到额外的预防效果。
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引用次数: 1
Microbiological evaluation of probiotic therapy in patients with pulmonary tuberculosis 肺结核患者益生菌治疗的微生物学评价
Pub Date : 2023-08-06 DOI: 10.15789/2220-7619-meo-7223
L. Otdushkina, Y. Zakharova, Artem A. Kholodov, T. V. Pyanzova
Patients with pulmonary tuberculosis and multiple pathogen resistance (MDR) develop persistent disorders of the intestinal microbiome during prolonged multicomponent chemotherapy requiring correction. However, there is limited data on the use of bacterial drugs in patients with tuberculosis followed by assessing their effectiveness. The aim of the study was to evaluate changes in the intestinal microbiome after a course of probiotics along with anti-tuberculosis chemotherapy in patients with MDR tuberculosis. Materials and methods. The design a prospective small-cohort study (n = 30). Patients with pulmonary tuberculosis received anti-tuberculosis drugs according to the IV or V regimen, the median of the doses taken was 34.5 (30; 57.5); gastrointestinal syndrome was recorded in all study subjects. Probiotic therapy was applied by using a preparation containing Bifidobacterium bifidum and B. animalis and Lactobacillus casei, L. plantarum, L. delbrueckii subsp.bulgaricus, L. acidophilus. The course of therapy comprised 21 days,1 capsule twice a day. Before and 7 days after probiotics therapy, studies on composition of the intestinal microbiota were carried out, the frequency of virulence factors Enterococcus spp., Staphylococcus spp., Candida spp. was examined; fatty acid composition and activity of enterococcal organic acid production were studied. Results. After a course of probiotics, a significant increase in lactobacillus titers was recorded from 5.2 (4.0; 6.0) to 6.1 (6.0; 8.0) lg CFU/g (p = 0.05). The frequency of mucosal colonization by Candida fungi and lactose-negative Escherichia decreased by 2-fold (p = 0.001) and 3-fold (p = 0.05), respectively. The frequency of detected virulent strains significantly decreased: hemolysin-producing staphylococci by 9 times (p = 0.009), enterococci with gelatinase activity by 6 times. E. faecalis membrane oleic acid level significantly increased (C9-C18:1) (p = 0.03). In E. faecium, cis-7-palmitoleic acid (C7-C16:1) and oleic (C9-C18:1) fatty acid level increased by 2-fold (p = 0.05), and for linoleic acid (C18:2) by 4 time (p = 0.04) accompanied by elevated acid formation by 1.5 times. Conclusion. A single course of probiotic therapy in patients with pulmonary tuberculosis leads to qualitative microbiome changes, which are characterized by decreased levels of conditionally pathogenic microorganisms with virulent properties and altered composition of the enterococcal cell membrane accompanied by their increased biochemical activity.
肺结核和多重病原体耐药(MDR)患者在长时间的多组分化疗期间出现持续的肠道微生物群紊乱,需要纠正。然而,在结核病患者中使用细菌药物并评估其有效性的数据有限。该研究的目的是评估耐多药结核病患者在服用益生菌和抗结核化疗一个疗程后肠道微生物群的变化。材料和方法。设计一项前瞻性小队列研究(n = 30)。肺结核患者按IV或V方案接受抗结核药物治疗,中位剂量为34.5 (30;57.5);所有研究对象均记录了胃肠道综合征。采用含有两歧双歧杆菌、动物双歧杆菌和干酪乳杆菌、植物乳杆菌、德尔布鲁氏乳杆菌亚种的制剂进行益生菌治疗。保加利亚嗜酸乳杆菌。疗程为21天,每日2次,1粒。研究益生菌治疗前和治疗后7 d肠道菌群组成,检测肠球菌、葡萄球菌、念珠菌等毒力因子的出现频率;研究了肠球菌脂肪酸组成及产有机酸活性。结果。经过一个疗程的益生菌治疗后,乳酸菌滴度从5.2 (4.0;6.0)到6.1 (6.0;8.0) lg CFU/g (p = 0.05)。念珠菌和乳糖阴性埃希氏菌的粘膜定植频率分别下降了2倍(p = 0.001)和3倍(p = 0.05)。检测到的毒力菌株频率显著降低:产溶血素葡萄球菌减少了9倍(p = 0.009),具有明胶酶活性的肠球菌减少了6倍。粪肠球菌膜油酸水平显著升高(C9-C18:1) (p = 0.03)。粪肠菌中顺式-7-棕榈油酸(C7-C16:1)和油酸(C9-C18:1)脂肪酸含量增加了2倍(p = 0.05),亚油酸(C18:2)脂肪酸含量增加了4倍(p = 0.04),产酸量增加了1.5倍。结论。肺结核患者单疗程的益生菌治疗可导致定性微生物组变化,其特征是具有毒性的条件致病性微生物水平降低,肠球菌细胞膜组成改变,并伴有生化活性增加。
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引用次数: 0
Evaluation of virus-neutralizing antibody level after novel coronavirus infection COVID-19: development of an instant assay assessing protective antibodies using a pseudovirus-based reaction 新型冠状病毒感染COVID-19后病毒中和抗体水平的评估:利用基于假病毒的反应开发一种评估保护性抗体的即时检测方法
Pub Date : 2023-08-06 DOI: 10.15789/2220-7619-eov-4336
Andrey A. Funtikov, Наталия A. Litvinova, E. Zuev, S. Kulemzin, Rachim R. Shukurov
The continued emergence of SARS-CoV-2 variants with immune evasion properties of concern, such as Delta (B.1.617.2) and Omicron (B.1.1.529), calls into question the extent of the antibody-mediated immune response from the virus. The presence of virus-neutralizing antibodies against SARS-CoV-2 in the blood serum of recovered and immunized volunteers is the most accurate indicator of the level of protective activity. Methods for reliable, sensitive and rapid detection of anti-SARS-CoV-2 nAbs are needed for preclinical and clinical vaccine research. In addition, quantification of virus-neutralizing antibodies in recovered COVID-19 subjects may be useful in identifying potential donors for passive immunization and therapeutic use of class G immunoglobulins. Pseudoviruses are actively used as an alternative to infectious viral isolates of pathogenicity groups III in serological studies to determine the titers of neutralizing antibodies formed in vaccinated or infected volunteers. In addition, using several pseudotypes with different reporter genes, it is possible to simultaneously detect antibodies to different types of viruses in one biological sample. Currently, the pseudolentiviral system is widely used, in which pseudoviral particles are obtained by transfection of producer cells with vectors of a multiplasmid system of 45 plasmids: one for the vector genome, the second for Gag-Pol, the third for Rev, and one or two for protein(s) envelope, or for the co-expression of a labeled viral protein such as GAG-GFP or VPR-GFP, the main advantage of which is safety due to the minimal risk of generating a replication-competent virus. The article discusses the development of a technique that allows to determine the presence of virus-specific neutralizing antibodies to the SARS-CoV-2 antigen in the blood serum of volunteers who have had a new coronavirus infection COVID-19 and/or immunized with specific prophylaxis drugs, healthy volunteers in a neutralization reaction on a HEK 293-cell culture. T-hAce2 using pseudotyped viral constructs based on human immunodeficiency virus. The results of the development and validation of the method, as well as its subsequent prospects for use, are shown.
具有令人担忧的免疫逃避特性的SARS-CoV-2变体,如Delta (B.1.617.2)和Omicron (B.1.1.529)的不断出现,令人质疑该病毒抗体介导的免疫反应的程度。在康复和免疫志愿者的血清中存在针对SARS-CoV-2的病毒中和抗体是最准确的保护活性水平指标。临床前和临床疫苗研究需要可靠、灵敏、快速的抗sars - cov -2抗体检测方法。此外,在康复的COVID-19受试者中定量检测病毒中和抗体,可能有助于确定被动免疫和治疗使用G类免疫球蛋白的潜在供体。在血清学研究中,假病毒被积极用于替代致病性III组的感染性病毒分离物,以确定接种疫苗或感染志愿者中形成的中和抗体的滴度。此外,使用几种具有不同报告基因的假病毒,可以在一个生物样本中同时检测到针对不同类型病毒的抗体。pseudolentiviral系统广泛应用,目前在pseudoviral粒子获得生产商的转染细胞的向量multiplasmid系统45质粒:一个用于矢量基因组,gag pol第二个,第三个牧师,和一个或两个蛋白(s)信封,或标记病毒蛋白的co-expression GAG-GFP或VPR-GFP等,这是安全的主要优势由于最小生成replication-competent病毒的风险。本文讨论了一种技术的发展,该技术可以确定患有新型冠状病毒感染COVID-19和/或接种特定预防药物的志愿者血清中是否存在针对SARS-CoV-2抗原的病毒特异性中和抗体,健康志愿者在HEK 293细胞培养中进行中和反应。利用基于人类免疫缺陷病毒的假型病毒构建T-hAce2。最后介绍了该方法的开发和验证结果,以及后续的应用前景。
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引用次数: 0
Antibiotics hypersensitivity reactions during COVID-19 pandemic COVID-19大流行期间的抗生素过敏反应
Pub Date : 2023-08-06 DOI: 10.15789/2220-7619-ahr-8062
Zaruhi G. Kalikyan
During the COVID-19 pandemic, there have emerged publications about various skin manifestations mainly caused by the related coronavirus, also including some case reports on dermal drug-related adverse reactions. In Armenia, the doctors in COVID-19 hospitals periodically consulted with allergists-immunologists regarding allergic conditions that many patients already suffered on admission or manifested after it. We present the series of three most interesting drug-induced cases with various skin manifestations in patients with COVID-19 pneumonia who requited antibiotic therapy. The causative significance of antibiotics was assessed according to Naranjos algorithm. In the first case (a 58-year-old female patient), a diagnosis of maculopapular exanthem was made based on the clinical picture. Although the coronavirus per se can result in similar manifestations, previous history of allergic reaction to ampicillin led to the conclusion that ceftriaxone (both are beta-lactam antibiotics) was the most probable cause. The second case (a 53-year-old male patient), clinically manifested as vasculitis, caused some difficulties because this is quite often skin manifestations related to SARS-CoV-2, and is rarely induced by medications. Taking into account the history of reaction to beta-lactam antibiotic, as well as the fact that the patient took amoxicillin without a prescription before hospitalization and with overt skin lesions at that time, amoxicillin was assessed as a possible cause. In the third case (a 64-years-old female patient), diagnosed with a bullous drug-induced skin eruption, despite isolated cases of such lesions can be manifestations of SARS-CoV-2 infection, moxitec (fluoroquinolone antibiotic) was assessed as the most probable cause, especially taking into account herpes in history. According to current recommendations, an issue of drug tests was discussed with all three patients to confirm the causative significance of indicated drugs and/or to select an alternative drug, if necessary. In this regard, the subjects were included in the database of patients with severe drug hypersensitivity reactions by their informed consent.
在2019冠状病毒病大流行期间,出现了主要由相关冠状病毒引起的各种皮肤表现的出版物,也包括一些皮肤药物相关不良反应的病例报告。在亚美尼亚,COVID-19医院的医生定期向过敏症专家和免疫学家咨询许多患者入院时或入院后出现的过敏症状。我们报告了三个最有趣的药物诱导的病例,这些病例在接受抗生素治疗的COVID-19肺炎患者中有不同的皮肤表现。根据Naranjos算法评估抗生素的致病意义。第一个病例(一名58岁的女性患者),根据临床表现诊断为黄斑丘疹。虽然冠状病毒本身可以导致类似的表现,但之前对氨苄西林的过敏反应史导致的结论是头孢曲松(都是β -内酰胺类抗生素)是最可能的原因。第二例患者(53岁男性)临床表现为血管炎,由于这通常是与SARS-CoV-2相关的皮肤表现,并且很少由药物引起,因此引起了一些困难。考虑到患者对β -内酰胺类抗生素的反应史,以及患者在住院前无处方服用阿莫西林和当时有明显的皮肤病变,评估阿莫西林是可能的原因。在第三例(64岁女性患者)中,诊断为药物引起的大疱性皮肤疹,尽管孤立病例的这种病变可能是SARS-CoV-2感染的表现,但评估莫西特(氟喹诺酮类抗生素)是最可能的原因,特别是考虑到病史中的疱疹。根据目前的建议,与所有三名患者讨论了药物测试的问题,以确认所指药物的致病意义和/或在必要时选择替代药物。在这方面,受试者经知情同意纳入严重药物超敏反应患者数据库。
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引用次数: 0
The effect of Saposin D on the anti-tuberculosis immune response in experimental tuberculosis infection 皂苷D对实验性结核感染抗结核免疫应答的影响
Pub Date : 2023-08-06 DOI: 10.15789/2220-7619-teo-2029
G. Shepelkova, V. Evstifeev, V. Avdienko, I. Bocharova, V. Yeremeev
Saposins (Sap) are a subgroup of glycoproteins belonging to the Saposin-Like Proteins family. They are generated by the proteolytic processing of the common precursor prosaposin. Saposins localize primarily in the lysosomes and are required for the catabolism of glycosphingolipids. Saposins are involved in the presentation of lipid mycobacterial antigens on CD1 molecules. SapD is the most abundant saposin in normal tissues, where its concentration is three times higher than that of other saposins. SapD promotes the hydrolysis of ceramide by acid ceramidase in vivo, as evidenced by the accumulation of -hydroxyl-ceramide in the kidneys and cerebellum of SapD-deficient mice. Accordingly, SapD-deficient animals show renal tubular degeneration and hydronephrosis, as well as progressive loss of Purkinje cells in the cerebellum, leading to ataxia. To date, no hereditary SapD deficiency has been identified in humans.Previously we had shown that macrophages derived from SAPD knockout mice suppress the growth of M. tuberculosis to a lesser extent than macrophages from wild-type mice. Moreover, compensation for the deficiency of SapD in knockout cells led to the restoration of their bactericidal function. Thus, SapD is an important component in the anti-TB immune response. However, it is not clear how SapD deficiency affects the in vivo antituberculosis immune response. In the model of experimental tuberculosis infection, it was shown that five weeks post infection the mycobacterial load in the lungs and spleens was significantly higher in SapD-ko mice than in wild-type mice. Analysis of the lung tissue cellular composition showed the differences between SapD-ko and B6 mice. Thus naive SapD-ko mice are characterized by a larger quantity of macrophages compared to B6 mice. It was also shown that five weeks after infection, SapD-ko mice differ from wild-type mice in a more pronounced neutrophilic infiltration of the lung tissue. A study of the propensity for apoptosis of cells in the lung tissue of SapD-ko mice showed that the content of apoptotic cells in the lungs of SapD knockout mice three weeks after infection was significantly higher than in wild-type B6 mice. Thus, SapD deficiency leads to a significant increase in inflammation during experimental tuberculosis infection, and also affects the predisposition of lung cells to apoptosis.
皂苷(Saposins, Sap)是糖蛋白的一个亚群,属于皂苷样蛋白家族。它们是由共同前体丙苷的蛋白水解过程产生的。皂苷主要存在于溶酶体中,是糖鞘脂分解代谢所必需的。皂苷参与脂质分枝杆菌抗原在CD1分子上的呈递。SapD是正常组织中含量最多的皂苷,其浓度是其他皂苷的3倍。SapD在体内促进酸性神经酰胺酶对神经酰胺的水解,SapD缺陷小鼠肾脏和小脑中-羟基神经酰胺的积累证明了这一点。因此,sapd缺乏的动物表现为肾小管变性和肾积水,以及小脑浦肯野细胞的进行性损失,导致共济失调。迄今为止,在人类中尚未发现遗传性SapD缺乏症。先前我们已经证明,来自SAPD敲除小鼠的巨噬细胞对结核分枝杆菌生长的抑制程度低于来自野生型小鼠的巨噬细胞。此外,对敲除细胞中SapD缺失的补偿导致其杀菌功能的恢复。因此,SapD是抗结核免疫应答的重要组成部分。然而,SapD缺乏如何影响体内抗结核免疫反应尚不清楚。在实验性结核感染模型中,结果显示,感染后5周,SapD-ko小鼠肺和脾脏的分枝杆菌负荷明显高于野生型小鼠。肺组织细胞组成分析显示SapD-ko和B6小鼠之间存在差异。因此,与B6小鼠相比,幼稚的SapD-ko小鼠具有更多的巨噬细胞。研究还表明,感染五周后,SapD-ko小鼠的肺组织中性粒细胞浸润比野生型小鼠更明显。对SapD-ko小鼠肺组织细胞凋亡倾向的研究表明,感染后3周,SapD敲除小鼠肺组织中凋亡细胞的含量明显高于野生型B6小鼠。因此,SapD缺乏导致实验性结核感染期间炎症显著增加,也影响肺细胞的凋亡倾向。
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引用次数: 0
Autoimmune streptococcal glomerulonephritis: the problem of nephritogenicity of Streptococcus pyogenes 自身免疫性链球菌性肾小球肾炎:化脓性链球菌致肾性问题
Pub Date : 2023-08-06 DOI: 10.15789/2220-7619-asg-8491
L. Burova, A. Suvorov, P. Pigarevsky, A. Totolian
Acute post-streptococcal glomerulonephritis usually occurs as a complication after a streptococcal infection due to untimely or inadequate antibiotic therapy. The etiology of post-streptococcal glomerulonephritis has been studied rather comprehensively. Today, both clinicians and microbiologists do not deny the dominant role of Streptococcus pyogenes (streptococcus attributed to serological group A, GAS). Usually, emergence of acute post-streptococcal glomerulonephritis (APSGN) is associated with the so-called GAS-related "nephritogenicity" often judged by appearance and accumulation of antibodies to the antigens and extracellular products of streptococcal cells in patient blood. This interpretation is quite loose and most likely evidence about a link to the bacterial strain, rather than its nephritogenicity. Many studies refer and still attribute a leading role of "nephritogenic" factors to various streptococcal antigens and related biologically active products. Streptococcal nephritogenic factors include cross-reacting antigens, streptokinase, cysteine proteinase, endostreptosin a GAS cell membrane protein as well as plasmin-tropic enzyme glyceraldehyde-3-phosphate dehydrogenase. Nephritogenicity of all such streptococcal products is suspected to result from the fact that they are found in renal biopsies like specific patient blood serum antibodies. Regarding a term of nephritogenicity, it has been evidenced that it cannot be attributed to any specific streptococcal cell product. This review attempted to analyze a number of bacterial products as starting factors triggering this process. APSGN can be reproduced experimentally in rabbits by intravenous administration of a heat-killed Streptococcus pyogenes culture. In our experiments, strains of serotypes 1, 4, 12, 15, 22 were used. They produced M-proteins and had the ability to bind human and rabbit immunoglobulin G by interacting with the Fc part of the IgG molecule. In numerous series of experiments, evidence was obtained regarding the initiating role of GAS IgGFc-receptor proteins in developing APSGN. Recent studies confirmed the role of streptococcal IgGFc-binding proteins in the initiation of glomerulonephritis after animals were inoculated with temperature-killed IgGFc-positive GAS. This approach excluded a large group of bacterial extracellular agents from the list of APSGN-initiating candidates. An unconventional view on the pathogenesis of GAS-infection-coupled complications may allow approaching their prevention or new treatment strategies.
急性链球菌感染后肾小球肾炎通常是由于抗生素治疗不及时或不充分导致的链球菌感染并发症。链球菌感染后肾小球肾炎的病因学研究比较全面。今天,临床医生和微生物学家都不否认化脓性链球菌(链球菌归因于血清学A组,GAS)的主导作用。通常,急性链球菌后肾小球肾炎(APSGN)的出现与所谓的gas相关的“肾原性”有关,通常通过患者血液中链球菌细胞抗原抗体和细胞外产物的外观和积累来判断。这种解释是相当松散的,最有可能的证据是与细菌菌株有关,而不是其肾原性。许多研究仍将“致肾”因子的主导作用归因于各种链球菌抗原及其相关的生物活性产物。链球菌的肾源性因子包括交叉反应抗原、链激酶、半胱氨酸蛋白酶、内链蛋白酶(GAS细胞膜蛋白)以及促纤溶酶甘油醛-3-磷酸脱氢酶。所有这些链球菌产物的致肾性被怀疑是由于它们在肾活检中被发现,如特异性患者血清抗体。关于肾源性的术语,已经证明它不能归因于任何特定的链球菌细胞产物。这篇综述试图分析一些细菌产物作为触发这一过程的启动因素。通过静脉注射热灭活化脓性链球菌培养物,可以在家兔实验中复制APSGN。本实验选用血清型1、4、12、15、22株。他们产生了m蛋白,并通过与IgG分子的Fc部分相互作用,具有结合人和兔免疫球蛋白G的能力。在一系列的实验中,已经获得了GAS iggfc受体蛋白在APSGN发生中的启动作用的证据。最近的研究证实了链球菌iggfc结合蛋白在动物接种温度杀死的iggfc阳性GAS后引发肾小球肾炎的作用。这种方法从apsgn启动候选药物列表中排除了一大批细菌细胞外药物。关于气体感染耦合并发症的发病机制的非常规观点可能允许接近其预防或新的治疗策略。
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引用次数: 1
A relation between specific immune status indicators and activity of “lipid peroxidation — antioxidant defense” system in COVID-19 neonates 新冠肺炎新生儿特异性免疫状态指标与“脂质过氧化-抗氧化防御”系统活性的关系
Pub Date : 2023-08-06 DOI: 10.15789/2220-7619-arb-8057
L. Rychkova, M. Darenskaya, A. Petrova, N. Semenova, E. Moskaleva, S. Kolesnikov, Anastasya S. Vanyarkina, L. Kolesnikova
The 2019 coronavirus infection (COVID-19) has not been considered as a solved issue for public health. Pregnant women and newborns are specifically vulnerable to COVID-19 infection compared to older children and healthy young adults. Virtually no data on relation between diverse arms of immunity in patients in neonatal period and coronavirus infection are available. The obtained results can contribute to a better understanding of the pathogenetic mechanisms on reactivity of immune processes in young patients and corresponding formation of approaches for prevention and correction of such disorders. The aim of the study was to determine magnitude of specific altered parameters in immune system and their relation with lipid peroxidation parameters in COVID-19 newborns. Two groups of newborns (mean age 43.1 days) were examined: SARS-CoV-2-positive (COVID-19 patients, n = 44) and negative (control group, n = 80) PCR test of nasopharyngeal swab. All newborns were assessed for specific indicators of peripheral blood immune status and lipid peroxidation activity. The concentration of Th1-pro-inflammatory cytokines and Th2-anti-inflammatory interleukins was assessed by enzyme immunoassay method (a panel of monoclonal antibodies). Spectrophotometric, fluorometric and enzyme immunoassay methods to evaluate the lipid peroxidation system were used. According to our data, newborns with COVID-19 vs. healthy newborns had decreased CRP, pro-inflammatory cytokines TNF, IL-1, IL-6, IL-8, and anti-inflammatory factor (IL-4). Change in lipid peroxidation system in children with COVID-was 19 related to higher level of DC, KD and CT, TBARs, increased SOD activity and reduced GPO. Numerous intersystem dependencies in the group of newborns with COVID-19 (CRP Total AOA, IL-4 KD and CT, IL-4 TBARs, IL-4 Total AOA, IL-4 SOD, IL-8 SOD, IFN GSH) were noted. It can be concluded that in newborns with COVID-19, changes in the immune system are nonspecific and are accompanied by an increased intensity of lipid peroxidation reactions against the background of reduced values of pro- and anti-inflammatory cytokines. These results may contribute to a more accurate assessment of intensity and dynamics of emerging neonatal coronavirus infection, which should be an important arm in preventing subsequent complications.
2019冠状病毒感染(COVID-19)尚未被视为公共卫生问题的解决方案。与年龄较大的儿童和健康的年轻人相比,孕妇和新生儿特别容易感染COVID-19。几乎没有关于新生儿期患者不同免疫臂与冠状病毒感染之间关系的数据。所得结果有助于更好地了解年轻患者免疫过程反应性的发病机制,并形成相应的预防和纠正此类疾病的方法。本研究的目的是确定COVID-19新生儿免疫系统特异性参数改变的程度及其与脂质过氧化参数的关系。检测两组新生儿(平均年龄43.1 d): sars - cov -2阳性(COVID-19患者,n = 44)和鼻咽拭子PCR检测阴性(对照组,n = 80)。评估所有新生儿外周血免疫状态和脂质过氧化活性的具体指标。采用酶免疫分析法(单克隆抗体组)测定th1促炎细胞因子和th2抗炎白细胞介素的浓度。采用分光光度法、荧光法和酶免疫分析法对脂质过氧化体系进行评价。根据我们的数据,与健康新生儿相比,患有COVID-19的新生儿CRP、促炎细胞因子TNF、IL-1、IL-6、IL-8和抗炎因子(IL-4)均降低。covid - 19患儿脂质过氧化系统的改变与DC、KD、CT、TBARs水平升高、SOD活性升高、GPO降低有关。注意到新生儿COVID-19组的许多系统间依赖性(CRP总AOA, IL-4 KD和CT, IL-4 TBARs, IL-4总AOA, IL-4 SOD, IL-8 SOD, IFN GSH)。由此可见,在COVID-19新生儿中,免疫系统的变化是非特异性的,伴随着脂质过氧化反应强度的增加,促炎性和抗炎性细胞因子的值降低。这些结果可能有助于更准确地评估新发新生儿冠状病毒感染的强度和动态,这应该是预防后续并发症的重要手段。
{"title":"A relation between specific immune status indicators and activity of “lipid peroxidation — antioxidant defense” system in COVID-19 neonates","authors":"L. Rychkova, M. Darenskaya, A. Petrova, N. Semenova, E. Moskaleva, S. Kolesnikov, Anastasya S. Vanyarkina, L. Kolesnikova","doi":"10.15789/2220-7619-arb-8057","DOIUrl":"https://doi.org/10.15789/2220-7619-arb-8057","url":null,"abstract":"The 2019 coronavirus infection (COVID-19) has not been considered as a solved issue for public health. Pregnant women and newborns are specifically vulnerable to COVID-19 infection compared to older children and healthy young adults. Virtually no data on relation between diverse arms of immunity in patients in neonatal period and coronavirus infection are available. The obtained results can contribute to a better understanding of the pathogenetic mechanisms on reactivity of immune processes in young patients and corresponding formation of approaches for prevention and correction of such disorders. The aim of the study was to determine magnitude of specific altered parameters in immune system and their relation with lipid peroxidation parameters in COVID-19 newborns. Two groups of newborns (mean age 43.1 days) were examined: SARS-CoV-2-positive (COVID-19 patients, n = 44) and negative (control group, n = 80) PCR test of nasopharyngeal swab. All newborns were assessed for specific indicators of peripheral blood immune status and lipid peroxidation activity. The concentration of Th1-pro-inflammatory cytokines and Th2-anti-inflammatory interleukins was assessed by enzyme immunoassay method (a panel of monoclonal antibodies). Spectrophotometric, fluorometric and enzyme immunoassay methods to evaluate the lipid peroxidation system were used. According to our data, newborns with COVID-19 vs. healthy newborns had decreased CRP, pro-inflammatory cytokines TNF, IL-1, IL-6, IL-8, and anti-inflammatory factor (IL-4). Change in lipid peroxidation system in children with COVID-was 19 related to higher level of DC, KD and CT, TBARs, increased SOD activity and reduced GPO. Numerous intersystem dependencies in the group of newborns with COVID-19 (CRP Total AOA, IL-4 KD and CT, IL-4 TBARs, IL-4 Total AOA, IL-4 SOD, IL-8 SOD, IFN GSH) were noted. It can be concluded that in newborns with COVID-19, changes in the immune system are nonspecific and are accompanied by an increased intensity of lipid peroxidation reactions against the background of reduced values of pro- and anti-inflammatory cytokines. These results may contribute to a more accurate assessment of intensity and dynamics of emerging neonatal coronavirus infection, which should be an important arm in preventing subsequent complications.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87985349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tick-borne infections in the south of Russia: modern epidemiological situation, new approach to create “forecasting” and “explaining” morbidity models (in astrakhan rickettsiosis fever and crimean-congo hemorrhagic fever) 俄罗斯南部蜱传感染:现代流行病学形势,建立“预测”和“解释”发病率模型的新方法(阿斯特拉罕立克次体热和克里米亚-刚果出血热)
Pub Date : 2023-08-06 DOI: 10.15789/2220-7619-tbi-2036
Darya A. Prislegina, O. V. Maletskaya, V. Dubyanskiy, Tatiana V. Taran, A. E. Platonov
The article presents a description of the current tick-borne infection epidemiological situation in the south of Russia from the years 2013 to 2022, proposes a new approach to develop forecasting models for morbidity dynamics of Astrakhan rickettsial fever (ARF) and Crimean hemorrhagic fever (СCHF) in the Astrakhan region and presents data assessing 2022 explaining models for the Stavropol Territory and Astrakhan Region. Materials and methods. A comprehensive research was performed using epidemiological analysis and non-parametric statistical methods. The data assessing tick-borne infections epidemic process manifestations were retrieved from ARF and CCHF morbidity databases (developed as a project) and documents of infectious disease focus epidemiological examination provided by the departments of Rospotrebnadzor in the subjects of the Southern and North Caucasian Federal Districts. Morbidity models were developed using the Bayes theorem and Walds sequential statistical analysis, with a preliminary calculation of indicators informativeness by the Kullback method. The values of climatic factors from the database of the Center for Collective Use IKI-monitoring of the Space Research Institute of the Russian Academy of Sciences were used. Results. The results of the study indicate persistence of serious epidemiological situation regarding rickettsiosis of the tick-borne spotted fever group, Q fever, tick-borne borreliosis and CCHF in the south of Russia. Almost all tick-borne infections nosological forms in children under 14 years (including young children and infants) were widely involved in the epidemic process, which belong to patients at risk for a complicated disease course due to complicated diagnostics and treatment. The annual registration of tick-borne infections cases in the resort areas, with the subsequent occurrence of imported cases in other, including non-endemic regions poses a serious problem. The proposed forecasting models allow to predict the CСHF and ARF morbidity for each administrative district of the Astrakhan region with up to 91.7% accuracy. The explaining models CСHF accuracy for the Stavropol Territory and Astrakhan Region, when tested in 2022, was 88.5 and 83.3%, respectively, for ARF 91.7%. Conclusions. The further continuation of forecasting and explaining models verification for planning preventive measures and propose similar steps for tick-borne borreliosis and Q fever to epidemiological tick-borne infections to stabilize situation in the south of Russia.
本文介绍了2013年至2022年俄罗斯南部蜱传感染流行病学现状,提出了一种开发阿斯特拉罕地区阿斯特拉罕立克次体热(ARF)和克里米亚出血热(СCHF)发病率动态预测模型的新方法,并提供了评估2022年斯塔夫罗波尔地区和阿斯特拉罕地区解释模型的数据。材料和方法。采用流行病学分析和非参数统计方法进行综合研究。评估蜱传感染流行过程表现的数据来自ARF和CCHF发病率数据库(作为一个项目开发的)和Rospotrebnadzor部门在南高加索和北高加索联邦区的受试者中提供的传染病焦点流行病学检查文件。采用贝叶斯定理和Walds序列统计分析建立发病率模型,并采用Kullback方法初步计算指标信息量。使用了俄罗斯科学院空间研究所集体使用iki监测中心数据库中的气候因子值。结果。研究结果表明,在俄罗斯南部,蜱传斑点热组立克次体病、Q热、蜱传伯氏螺旋体病和CCHF持续存在严重的流行病学情况。14岁以下儿童(包括幼儿和婴儿)中几乎所有蜱传感染的病原学形式都广泛参与流行过程,由于诊断和治疗复杂,属于病程复杂的患者。度假区每年登记的蜱传感染病例,随后在其他地区(包括非流行地区)出现输入性病例,构成一个严重问题。所提出的预测模型可以预测阿斯特拉罕地区每个行政区域的CСHF和ARF发病率,准确率高达91.7%。在2022年测试时,斯塔夫罗波尔领土和阿斯特拉罕地区的解释模型CСHF的准确性分别为88.5和83.3%,ARF为91.7%。结论。进一步继续预测和解释模型验证,以规划预防措施,并就蜱传borreliosis和Q热提出与流行病学蜱传感染类似的步骤,以稳定俄罗斯南部的局势。
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引用次数: 0
Characteristics of acute diarrhea in adult cases with Campylobacter spp. positive fecal samples 成人弯曲杆菌阳性急性腹泻的特点
Pub Date : 2023-08-06 DOI: 10.15789/2220-7619-coa-1886
E. Kozhukhova, N. Andreeva, M. Dmitrieva, Svetlana L. Nikilaenko
Recently, cases caused by Campylobacter spp. in Russia similar to other countries tended to clearly rise, partly due to the widely implemented biomolecular PCR-based laboratory analysis that substantially facilitated Campylobacter spp. detection in patients samples. The problem of being infected by Campylobacter spp. is so far worth studying because of campilbacteriosis signs in a form of a variety of clinical patterns including local and general forms, possible trigger role in forming the consequent chronic digestive tract pathology as well as general systemic pathology. Development of colitis or heamocolitis as the pattern part of acute diarrhea caused by Campylobacter spp. is usually considered as associated with the disease burden. So far as adult patients have acute diarrhea with positive Campylobacter spp. samples it might be of interest to compare and analyze their clinical and laboratory data to find some possible associations as particular features of different disease patterns. Objective to analyze clinical features and laboratory data of hospitalized AD adult cases with feces samples positive for Campylobacter spp. When carrying out the retrospective cohort study the analyzed were clinical and laboratory data of 111 hospitalized adult patients suffering from moderate acute diarrhea with clinical samples (feces) positive for Campylobacter spp. To verify acute infectious diarrhea all patients went through complex specific laboratory examination that included PCR based methods (feces) with use of Amplisense AD screen-FL in addition to routine standard culture (feces), serologic (specific antibody detection) and ELISA laboratory methods. The analysis results have shown that more than 1/2 part of patients developed colitis syndrome with blood in feces in practically every forth case. In patients (predominantly males) without chronic digestive tract problems relative risks to develop colitis and haemocolitis are respectively 1.6 and 2.6 times higher given they are hospitalized on day 4 after the onset and later versus those hospitalized earlier.
近年来,与其他国家类似,俄罗斯由弯曲杆菌引起的病例有明显上升的趋势,部分原因是广泛实施的基于生物分子pcr的实验室分析大大促进了患者样本中弯曲杆菌的检测。弯曲杆菌感染的问题是迄今为止值得研究的,因为弯曲杆菌病的症状表现为多种临床模式,包括局部和全身形式,可能在形成随后的慢性消化道病理和全身病理中起触发作用。弯曲杆菌引起的急性腹泻的典型部分是结肠炎或血性结肠炎的发展,通常被认为与疾病负担有关。对于弯曲杆菌阳性的急性腹泻成年患者来说,比较和分析他们的临床和实验室数据,以发现一些可能的关联,作为不同疾病模式的特定特征,可能是有意义的。目的分析成人AD成人粪便弯曲杆菌阳性住院病例的临床特征和实验室资料,在进行回顾性队列研究时,分析了111例成人中度急性腹泻患者临床标本(粪便)弯曲杆菌阳性住院患者的临床和实验室资料,为验证急性感染性腹泻,所有患者均进行了包括PCR为基础的复杂特异性实验室检查方法(粪便)除常规标准培养(粪便)、血清学(特异性抗体检测)和ELISA实验室方法外,采用Amplisense AD screen-FL。分析结果表明,几乎每4例患者中就有1/2以上的患者出现粪血结肠炎综合征。在没有慢性消化道问题的患者(主要是男性)中,发病后第4天住院的结肠炎和血结肠炎的相对风险分别比较早住院的患者高1.6倍和2.6倍。
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引用次数: 0
Adhesiveness of the specific phages to yersiniae cells assessed by optical trapping 用光学诱捕法评估特定噬菌体对耶尔森氏菌细胞的粘附性
Pub Date : 2023-08-06 DOI: 10.15789/2220-7619-aot-2086
I. Konyshev, L. Dudina, N. A. Morozova, A. Byvalov
In recent years, there has been increasing interest in using bacteriophages in the complex therapy of some infectious diseases. Objectively, it is related to the spread of antibiotic resistance and a small number of side effects triggered by phages applied locally and parenterally. Yersiniae are no exception to this rule, but their interaction with virions has not been studied thoroughly. In three types of lytic Yersiniae bacteriophages are used for diagnostic purposes, which differ in specificity, virulence, and morphological features. We evaluated the interaction force between phages and bacteriae by optical trapping. Materials and methods. Live Yersinia pseudotuberculosis and Y. pestis cells with different LPS structure and preparations of three bacteriophages Pokrovskayas phage, dHerelles phage (also named as the pseudotuberculosis phage) and the phage L-413C were used. The Pokrovskayas phage is well studied and widely used in diagnostics, but the mechanism of its adsorption on Y. pestis and Y. pseudotuberculosis cells is not well-understood. The phage L-413C lyses plague bacteria, while dHerrels phage can lyse both pathogens. Virions were linked to the surface of aminated glass. Optically trapped microbial cells were approached to the glass surface and then retracted in the opposite direction. The amplitude of the leap was recalculated into force through calibration coefficients. The primary data were processed in the program R; statistical analysis was performed using Matlab 7.0 and Statistica 12 Results and discussion. The analysis of histograms revealed the presence of a specific component in the Y. pseudotuberculosisdHerrells phage (Fmean = 7.463.52 pN) system, as well as in all pairs involving plague microbe. In the latter case, the interaction forces were comparable: 8.643.83 pN for dHerelles phage,11.034.22 pN for Pokrovskayas phage, and 10.424.79 pN for phage L-413C. The average detachment force from the substrate treated with bovine serum albumin (BSA) was comparable for both cell types. Our results convincingly prove an opportunity for using the optical trapping to estimate interaction force in other bacteriumphage systems.
近年来,利用噬菌体进行感染性疾病的综合治疗已引起人们越来越多的兴趣。客观上,它与抗生素耐药性的传播以及局部和非肠道应用噬菌体引发的少量副作用有关。耶尔森尼菌也不例外,但它们与病毒粒子的相互作用还没有得到彻底的研究。在三种类型的裂解耶尔森菌噬菌体用于诊断目的,其特异性,毒力和形态特征不同。我们用光学捕获法评估了噬菌体与细菌之间的相互作用力。材料和方法。采用不同LPS结构的假结核耶尔森氏菌和鼠疫耶尔森氏菌活细胞,制备三种噬菌体Pokrovskayas噬菌体、dHerelles噬菌体(又称假结核噬菌体)和噬菌体L-413C。Pokrovskayas噬菌体在诊断中得到了广泛的研究和应用,但其吸附鼠疫菌和假结核杆菌细胞的机制尚不清楚。噬菌体L-413C可以裂解鼠疫菌,而大肠杆菌噬菌体可以裂解这两种病原体。病毒粒子被连接到胺化玻璃的表面。光学捕获的微生物细胞靠近玻璃表面,然后向相反方向缩回。通过校正系数将跳跃幅度重新计算为力。原始数据在R程序中处理;使用Matlab 7.0和Statistica 12进行统计分析。直方图分析显示,假结核杆菌-赫氏噬菌体(Fmean = 7.463.52 pN)系统以及所有涉及鼠疫微生物的噬菌体对中存在一种特定成分。后一种情况下,相互作用力具有可比性:dHerelles噬菌体为8.643.83 pN, Pokrovskayas噬菌体为11.034.22 pN, L-413C噬菌体为10.424.79 pN。用牛血清白蛋白(BSA)处理的底物的平均脱离力对两种细胞类型是相当的。我们的结果令人信服地证明了利用光学捕获来估计其他噬菌体系统中的相互作用力的机会。
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Russian Journal of Infection and Immunity
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