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Features of laser Doppler flowmetry in patients with bacterial and viral (covid-19) community-acquired pneumonia 细菌性和病毒性(covid-19)社区获得性肺炎患者的激光多普勒血流特征
Pub Date : 2022-12-23 DOI: 10.36604/1998-5029-2022-86-68-72
O. Abuldinova
Introduction. As a result of the coronavirus infection (COVID-19) pandemic, almost 74.9 thousand people died of pneumonia in Russia in 2021. Community-acquired pneumonia (CAP) is accompanied by a systemic re­sponse of the body to inflammation in the lung tissue and disorder of microhemocirculation. The method of laser Doppler flowmetry (LDF) allows assessing the general parameters of the microcirculatory bed and determining the state of various factors regulating the nutritive flow.Aim. To conduct a comparative analysis of LDF indices in patients with COVID-19- associated and bacterial CAP.Materials and methods. 140 patients were examined, 100 of them with non-severe CAP (main group), and 40 patients with extrapulmonary pathology (comparison group). The main group included 44 people with bacterial CAP and 56 people with COVID-19-associated CAP. Bacteriological studies of sputum were performed; detection of SARS-CoV-2 RNA in swabs from the oropharynx and nasopharynx by PCR, LDF to assess the state of pe­ripheral blood flow was carried out.Results. In patients with COVID-19-associated CAP, compared with patients with bacterial CAP, a decrease in the microcirculation index by 1.26 times (p<0.0005), an increase in the coefficient of variation by 1.11 times (p<0.0005) was found.Conclusion. In patients with COVID-19-associated CAP, compared with patients with bacterial CAP, more significant pathological changes in Dopplerograms were detected, which may indicate more pronounced disorders in the microcirculatory bed in COVID-19-associated CAP caused by exposure to the SARS-COV- 2 virus. Perhaps the established fact can lead to adverse outcomes of the course of the disease.
介绍。由于冠状病毒感染(COVID-19)大流行,2021年俄罗斯有近7.49万人死于肺炎。社区获得性肺炎(CAP)伴随着机体对肺组织炎症和微循环紊乱的全身性反应。激光多普勒流量法(LDF)可以评估微循环床的一般参数,并确定调节营养流量的各种因素的状态。目的:对COVID-19相关性cap与细菌性cap患者LDF指标进行比较分析。共检查140例患者,其中非重度CAP患者100例(主组),肺外病理患者40例(对照组)。主要组包括44例细菌性CAP和56例covid -19相关CAP。对痰液进行细菌学研究;采用PCR、LDF法检测口咽和鼻咽拭子中SARS-CoV-2 RNA,评估外周血流状态。与细菌性CAP患者相比,covid -19相关性CAP患者微循环指数下降1.26倍(p<0.0005),变异系数增加1.11倍(p<0.0005)。在covid -19相关性CAP患者中,与细菌性CAP患者相比,多普勒图检测到更明显的病理改变,这可能表明暴露于SARS-COV- 2病毒导致的covid -19相关性CAP微循环床紊乱更为明显。也许既定的事实会导致疾病过程中的不良后果。
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引用次数: 0
Analysis of drug therapy for bronchial asthma 支气管哮喘的药物治疗分析
Pub Date : 2022-12-23 DOI: 10.36604/1998-5029-2022-86-138-148
Yefei Li, Wei Zhang, Xue Chen, Chenyou Pang
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引用次数: 0
Prospects for the pharmacological application of N-acyle-thanolamines of polyunsaturated fatty acids in the therapy of respiratory diseases on the example of bronchial asthma 多不饱和脂肪酸n -酰基乙醇胺在呼吸系统疾病治疗中的药理应用展望——以支气管哮喘为例
Pub Date : 2022-12-23 DOI: 10.36604/1998-5029-2022-86-129-137
I. Kovalenko, Y. K. Denisenko, T. Novgorodtseva, N. Bocharova, U. M. Omatova
Introduction. At present, the mechanisms of the processes of resolving chronic inflammation in asthma are not fully understood. A search for new pharmacological preparations and substances for the treatment and control of the course of asthma is required. Promising in this direction are N-acylethanolamines (NAE) of polyunsaturated fatty acids - bioactive lipid molecules that exhibit many signaling functions. NAEs are capable of influencing the synthesis of pro-inflammatory cytokines and are also appear to be a substrate for the synthesis of pro-permissive lipid signaling molecules. This review collects data on NAE, provides an overview, biosynthesis, and describes their anti-inflammatory effects.Aim. Summarizing the data of domestic and foreign researchers on the possibility of NAE in the treatment of respiratory diseases on the example of bronchial asthma.Materials and methods. The review uses data from articles published in PubMed, Google Scholar, eLIBRARY.Results. The study and compilation of literature on this issue made it possible to conclude that synthetic NAEs are promising pharmacological objects for asthma therapy, however, further testing of the anti-in­flammatory effects of NAEs and the establishment of the molecular mechanism of their action on inflammation processes are needed.
介绍。目前,解决哮喘慢性炎症过程的机制尚不完全清楚。需要寻找治疗和控制哮喘病程的新药理学制剂和物质。在这个方向上很有前途的是多不饱和脂肪酸的n -酰基乙醇胺(NAE) -具有许多信号功能的生物活性脂质分子。NAEs能够影响促炎细胞因子的合成,并且似乎也是促容许性脂质信号分子合成的底物。本文收集了有关NAE的资料,综述了其生物合成方法,并描述了其抗炎作用。以支气管哮喘为例,总结国内外研究者对NAE治疗呼吸系统疾病可能性的研究资料。材料和方法。该综述使用的数据来自PubMed、Google Scholar、eLIBRARY.Results等网站上发表的文章。通过对相关文献的研究和整理,可以得出结论:合成NAEs是治疗哮喘的有前景的药理学对象,但需要进一步测试NAEs的抗炎作用,并建立其作用于炎症过程的分子机制。
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引用次数: 0
Morphological structure of cotyledons with non-contrasted blood vessels in the placenta of women who had an exacerbation of mono- and mixed-cytomegalovirus infection in the second trimester of pregnancy 妊娠中期单纯性和混合性巨细胞病毒感染加重的妇女胎盘中子叶与未对比血管的形态结构
Pub Date : 2022-12-23 DOI: 10.36604/1998-5029-2022-86-80-90
I. Gorikov
Aim. To assess the morphological structure of cotyledons with non-contrasted blood vessels in the pla­centas in women who had an exacerbation of mono- and mixed cytomegalovirus infection (CMVI) in the second trimester of pregnancy.Materials and methods. The histometric parameters of the villi were studied with different visualization on X-ray phlebograms of blood vessels in 112 cotyledons of placentas in women with pregnancy, uncomplicated and com­plicated by mono- and mixed-CMVI (combination of CMVI and reactivation of chronic herpes virus infection type 1 HSV). The first group (control) included 36 cotyledons with a clear contrasting of the vascular bed in the placentas from women with an uncomplicated gestational period. The main group was represented by 76 cotyledons: subgroup 2a - 24 cotyledons, in which the bloodstream was not detected, in placentas from patients with exacerbation of mono-CMVI as­sociated with chronic subcompensated placental insufficiency (CSPI); subgroup 2b - 16 cotyledons with blood vessels not diagnosed by X-ray phlebography, in placentas from women with mixed CMVI infection, initiating the development of CSPI; subgroup 3a - 21 cotyledons with non-contrasted bloodstream in placentas from patients with exacerbation of mono-CMVI and chronic decompensated placental insufficiency (CDPI); subgroup 3b - 15 cotyledons with a similar an­giographic picture in placentas from women who had an exacerbation of mixed CMVI in the second trimester of gestation and CDPI. Identification of cotyledons with a clear visualization of blood vessels and with a non-contrasted vascular bed in the marginal part of the placenta was carried out by dosed administration of minium on linseed oil (1:3) through the vein of umbilical cord and assessment of the angiographic picture on X-ray, which were obtained using the RUM-20M apparatus with X-ray image amplifier Sapphire (Russia). For histological analysis, tissue pieces were taken in the same places before and after injection of the contrast mass into the bloodstream of the organ, on the damaged areas of which clamps were applied.Results. In the first group, the cotyledons had clear contours of the blood vessels and the vein draining them. Avascular villi (AV) accounted for 2.05±0.22%, villi with syncytiocapillary membranes (SCM) - 33.5±2.41%, villi with one (1) SCM - 77.1±2.07%, with two (2) SCM - 20.9±1.98% and with three (3) SCM - 1.42±0.09%. In subgroup 2a, compared with the first group, there was a deformation of the lumen of the vein of the stem villi of the I and II order, in which erythrocyte aggregates, single leukocytes and rarely thrombi were determined, as well as signs of edema and partial desquamation of endotheliocytes, fibrinoid and inflammatory changes in the vessel wall. The number of AV increased (by 6.87 times, p<0.001) and the number of villi with SCM decreased (by 2.05 times, p<0.001) with no significant differences between villi with 1, 2, and 3 SCM. In subgroup 2b, in compariso
的目标。评估妊娠中期单纯性和混合性巨细胞病毒感染(CMVI)加重的妇女的子叶形态结构和未对比血管。材料和方法。本文对112例妊娠妇女胎盘子叶的血管x线静脉造影(单纯性和混合性CMVI合并CMVI和1型慢性疱疹病毒感染的再激活)中绒毛的组织学参数进行了研究。第一组(对照组)包括36个子叶,胎盘血管床的清晰对比来自无复杂妊娠期的妇女。主要组由76个子叶代表:亚组2a - 24个子叶,其中未检测到血流,这些子叶来自与慢性亚代偿性胎盘功能不全(CSPI)相关的单核cmvi加重患者的胎盘;混合CMVI感染妇女胎盘中,2b - 16子叶伴血管未被x线静脉造影诊断,引发CSPI的发展;来自单核cmvi加重和慢性失代偿性胎盘功能不全(CDPI)患者的无对比血流的3a - 21子叶亚组;亚组3b - 15子叶在妊娠中期混合性CMVI和CDPI加重的妇女胎盘中具有相似的地理图像。通过脐带静脉给药微量亚麻籽油(1:3),并对x射线血管造影图像进行评估,鉴定子叶血管清晰,胎盘边缘无对比血管床,使用带有蓝宝石(俄罗斯)x射线图像放大器的RUM-20M仪器。为了进行组织学分析,在将造影剂注射到器官血流中之前和之后,在相同的地方取组织片,在受损部位应用夹钳。在第一组中,子叶有清晰的血管轮廓和引流它们的静脉。无血管绒毛(AV)占2.05±0.22%,有合胞毛细膜(SCM)的绒毛占33.5±2.41%,有一(1)膜的绒毛占77.1±2.07%,有二(2)膜的绒毛占20.9±1.98%,有三(3)膜的绒毛占1.42±0.09%。在2a亚组中,与第一组相比,I和II目干绒毛静脉管腔变形,其中红细胞聚集,单个白细胞,很少有血栓,内皮细胞水肿和部分脱屑,纤维蛋白样和血管壁炎症改变的迹象。1、2、3个SCM组绒毛的AV数增加(6.87倍,p<0.001),绒毛数减少(2.05倍,p<0.001),差异无统计学意义。在2b亚组中,与2a亚组相比,内皮中度折叠、部分脱屑面积、AV(1.39倍,p<0.01)和2个SCMs的绒毛(1.44倍,p<0.05)更为常见,而1个SCM的绒毛浓度降低(1.19倍,p<0.05)。在3b亚组中,与3a亚组相比,发现更多的血管不能从子叶突流出血液(12条,p<0.001),并呈弓形(10条,p<0.001),其中它们的数量分别为3条(p<0.001)和2条(p<0.001)。结果发现,血管内皮层的折叠更为明显,同时血管腔内也出现了ag聚集物、中性粒细胞、淋巴细胞和血栓。1个SCM组绒毛的发生率增加了1.13倍(p<0.05), 2个SCM组绒毛的发生率减少了1.67倍(p<0.05), 3个SCM组绒毛的发生率减少了2.13倍(p<0.001)。在3b亚组子叶中,与2b亚组相比,盲目终止血管较多(2次,p<0.05),静脉呈弓形走行(2.5次,p<0.05),管腔不均匀,核深染,细胞完全脱屑,血栓伴钙化,动脉管腔完全或部分闭塞,炎症,血管肌层纤维蛋白降解,钙盐沉积,以及AV(1.29次)。p<0.05),绒毛1次(1.40次,p<0.001);毛细管电泳检测绒毛的次数较少(1.35次,p<0.05), 2次(2.78次,p<0.001)和3次(1.57次,p<0.05)。在妊娠中期混合CMVI和CDPI加重的女性中,与单一CMVI再激活导致CDPI的患者相比,血管破坏和血管阻塞过程以及血管生成抑制在血管未显影的子叶中更为明显。
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引用次数: 0
Modulating effect of TRPA1 and TRPM8 channels on cytokine production by pro- and anti-inflammatory macrophages TRPA1和TRPM8通道对促炎性和抗炎性巨噬细胞产生细胞因子的调节作用
Pub Date : 2022-12-22 DOI: 10.36604/1998-5029-2022-86-33-39
O. Kotova, D. Gassan, D. Naumov, I. Sugaylo, Y. Gorchakova
Introduction. Transient receptor potential (TRP) channels expressed on many cells, including macro­phages, are an attractive target for pharmacological modulation for the treatment of various diseases. At the same time, currently available data on the functional role of TRP on macrophages are scarce.Aim. To establish the effect of TRPA1 and TRPM8 channels on the production of cytokines by macrophages during pro-inflammatory (M1) and anti-inflammatory (M2) polarization.Materials and methods. Macrophages were obtained from monocytes of 8 healthy donors by differ­entiation in the presence of GM-CSF or M-CSF. Cell polarization was achieved by adding to the culture medium 100 ng/ml LPS + IFN-y 20 ng/ml (M1) or IL-4 20 ng/ml (M2) for 24 h. In order to modulate TRP activity, cinnamaldehyde 100 цМ (TRPA1 agonist), HC-030031 100 цМ (TRPA1 blocker), WS-12 10 цМ (TRPM8 agonist), or RQ-00434739 1 цМ (TRPM8 blocker) were used.Results. It was found that during M1 polarization TRPA1 channels inhibited the pro­duction of CXCL10, and TRPM8 increased the level of IL-8. Under polarization to the М2 phenotype, TRPA1 suppressed the production of pro-inflammatory cytokines IL-ie, TNF-a, IL-6, IL-12p70 and IFN-y, and TRPM8 did not significantly affect the levels of the analyzed mediators.Conclusion. The obtained results indicate that in terms of cytokine production by macrophages, TRPA1 has a predominantly anti-inflammatory effect, while TRPM8 shows a limited influence, which come to the regulation of IL-8 synthesis.
介绍。瞬时受体电位(TRP)通道在许多细胞上表达,包括巨噬细胞,是一个有吸引力的靶点,用于各种疾病的药物调节治疗。同时,目前关于TRP对巨噬细胞的功能作用的资料很少。建立巨噬细胞促炎(M1)和抗炎(M2)极化过程中TRPA1和TRPM8通道对细胞因子产生的影响。材料和方法。在GM-CSF或M-CSF存在下,从8个健康供者的单核细胞中分化获得巨噬细胞。在培养基中加入100 ng/ml LPS + IFN-y 20 ng/ml (M1)或IL-4 20 ng/ml (M2),使细胞极化24 h。为了调节TRP活性,分别使用肉桂醛100 цМ (TRPA1激动剂)、HC-030031 100 цМ (TRPA1阻断剂)、WS-12 10 цМ (TRPM8激动剂)或RQ-00434739 1 цМ (TRPM8阻断剂)。结果发现,在M1极化过程中,TRPA1通道抑制CXCL10的产生,TRPM8通道增加IL-8的水平。极化至М2表型下,TRPA1抑制促炎因子IL-ie、TNF-a、IL-6、IL-12p70和IFN-y的产生,而TRPM8对所分析介质的水平无显著影响。结果表明,在巨噬细胞产生细胞因子方面,TRPA1主要具有抗炎作用,而TRPM8的影响有限,从而调控IL-8的合成。
{"title":"Modulating effect of TRPA1 and TRPM8 channels on cytokine production by pro- and anti-inflammatory macrophages","authors":"O. Kotova, D. Gassan, D. Naumov, I. Sugaylo, Y. Gorchakova","doi":"10.36604/1998-5029-2022-86-33-39","DOIUrl":"https://doi.org/10.36604/1998-5029-2022-86-33-39","url":null,"abstract":"Introduction. Transient receptor potential (TRP) channels expressed on many cells, including macro­phages, are an attractive target for pharmacological modulation for the treatment of various diseases. At the same time, currently available data on the functional role of TRP on macrophages are scarce.Aim. To establish the effect of TRPA1 and TRPM8 channels on the production of cytokines by macrophages during pro-inflammatory (M1) and anti-inflammatory (M2) polarization.Materials and methods. Macrophages were obtained from monocytes of 8 healthy donors by differ­entiation in the presence of GM-CSF or M-CSF. Cell polarization was achieved by adding to the culture medium 100 ng/ml LPS + IFN-y 20 ng/ml (M1) or IL-4 20 ng/ml (M2) for 24 h. In order to modulate TRP activity, cinnamaldehyde 100 цМ (TRPA1 agonist), HC-030031 100 цМ (TRPA1 blocker), WS-12 10 цМ (TRPM8 agonist), or RQ-00434739 1 цМ (TRPM8 blocker) were used.Results. It was found that during M1 polarization TRPA1 channels inhibited the pro­duction of CXCL10, and TRPM8 increased the level of IL-8. Under polarization to the М2 phenotype, TRPA1 suppressed the production of pro-inflammatory cytokines IL-ie, TNF-a, IL-6, IL-12p70 and IFN-y, and TRPM8 did not significantly affect the levels of the analyzed mediators.Conclusion. The obtained results indicate that in terms of cytokine production by macrophages, TRPA1 has a predominantly anti-inflammatory effect, while TRPM8 shows a limited influence, which come to the regulation of IL-8 synthesis.","PeriodicalId":9598,"journal":{"name":"Bulletin Physiology and Pathology of Respiration","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90193244","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
Peculiarities of TRP channels expression and cytokine profile of sputum in patients with chronic obstructive pulmonary disease and progressive bronchial obstruction 慢性阻塞性肺疾病伴进行性支气管梗阻患者痰中TRP通道表达及细胞因子谱的特点
Pub Date : 2022-12-22 DOI: 10.36604/1998-5029-2022-86-24-32
D. Naumov, I. Sugaylo, D. Gassan, O. Kotova, Y. Gorchakova, E. Sheludko
Introduction. Chronic obstructive pulmonary disease (COPD) is a pathology accompanied by a pro­gressive and irreversible deterioration in airway patency. It is known that macrophages of the respiratory tract are actively involved in the reorganization of the extracellular matrix leading to the development of bronchial remodeling.Aim. To assess the relationship between the progression rate of bronchial obstruction in COPD, the expression of TRP channels on alveolar macrophages, and the levels of inflammatory markers in the respiratory tract.Materials and methods. The study enrolled 37 patients with COPD, including 23 people with a FEV1 deterioration >50 ml/year and 14 with FEV1 decline <50 ml/year. The expression of TRPV1, TRPV4, TRPA1, TRPM8 channels was determined on alveolar macrophages by flow cytometry. Analysis of cytokines was performed in sputum supernatant by multiplex assay on a flow cytometer.Re­sults. It was found that in patients with progressive bronchial obstruction TRPV4 expression was significantly increased: 14.2 (10.8; 23.4)% vs. 8.6 (3.6; 15.4)% (p=0.03). In addition, in the general group of patients a highly significant inverse correlation was found between TRPV4 expression and the dynamics of FEV1 (p=-0.52, p<0.001). Patients with a decrease in FEV1 >50 ml/year were characterized by significantly elevated levels of IL-2, IL-4, IL-17A, IL-10, IL-12p70, CXCL10 and MCP-1. Additionally, we found that concentrations of several cytokines were directly correlated with TRPV4 expres­sion on macrophages: IL-4 (p=0.51, p=0.001), CXCL10 (p=0.59, p<0.001), MCP-1 (p=0.56, p<0.001), TGF-ei (p=0.42, p=0.009), IFN-y (p=0.37, p=0.02).Conclusion. TRPV4 channels expressed on alveolar macrophages are involved in the inflammatory process and airway remodeling in COPD, which is manifested by their relationships with the level of certain cytokines production, as well as the rate of the progression of bronchial obstruction.
介绍。慢性阻塞性肺疾病(COPD)是一种伴有气道通畅进行性和不可逆恶化的病理。我们知道,呼吸道巨噬细胞积极参与细胞外基质的重组,导致支气管重建的发生。探讨COPD支气管梗阻进展率与肺泡巨噬细胞TRP通道表达及呼吸道炎症标志物水平的关系。材料和方法。该研究招募了37例COPD患者,其中23例FEV1恶化(50 ml/年),14例FEV1下降(50 ml/年),其特征是IL-2、IL-4、IL-17A、IL-10、IL-12p70、CXCL10和MCP-1水平显著升高。此外,我们还发现巨噬细胞中IL-4 (p=0.51, p=0.001)、CXCL10 (p=0.59, p<0.001)、MCP-1 (p=0.56, p<0.001)、TGF-ei (p=0.42, p=0.009)、IFN-y (p=0.37, p=0.02)等细胞因子的浓度与TRPV4的表达有直接关系。肺泡巨噬细胞上表达的TRPV4通道参与COPD的炎症过程和气道重塑,表现为其与某些细胞因子的产生水平以及支气管梗阻进展速度的关系。
{"title":"Peculiarities of TRP channels expression and cytokine profile of sputum in patients with chronic obstructive pulmonary disease and progressive bronchial obstruction","authors":"D. Naumov, I. Sugaylo, D. Gassan, O. Kotova, Y. Gorchakova, E. Sheludko","doi":"10.36604/1998-5029-2022-86-24-32","DOIUrl":"https://doi.org/10.36604/1998-5029-2022-86-24-32","url":null,"abstract":"Introduction. Chronic obstructive pulmonary disease (COPD) is a pathology accompanied by a pro­gressive and irreversible deterioration in airway patency. It is known that macrophages of the respiratory tract are actively involved in the reorganization of the extracellular matrix leading to the development of bronchial remodeling.Aim. To assess the relationship between the progression rate of bronchial obstruction in COPD, the expression of TRP channels on alveolar macrophages, and the levels of inflammatory markers in the respiratory tract.Materials and methods. The study enrolled 37 patients with COPD, including 23 people with a FEV1 deterioration >50 ml/year and 14 with FEV1 decline <50 ml/year. The expression of TRPV1, TRPV4, TRPA1, TRPM8 channels was determined on alveolar macrophages by flow cytometry. Analysis of cytokines was performed in sputum supernatant by multiplex assay on a flow cytometer.Re­sults. It was found that in patients with progressive bronchial obstruction TRPV4 expression was significantly increased: 14.2 (10.8; 23.4)% vs. 8.6 (3.6; 15.4)% (p=0.03). In addition, in the general group of patients a highly significant inverse correlation was found between TRPV4 expression and the dynamics of FEV1 (p=-0.52, p<0.001). Patients with a decrease in FEV1 >50 ml/year were characterized by significantly elevated levels of IL-2, IL-4, IL-17A, IL-10, IL-12p70, CXCL10 and MCP-1. Additionally, we found that concentrations of several cytokines were directly correlated with TRPV4 expres­sion on macrophages: IL-4 (p=0.51, p=0.001), CXCL10 (p=0.59, p<0.001), MCP-1 (p=0.56, p<0.001), TGF-ei (p=0.42, p=0.009), IFN-y (p=0.37, p=0.02).Conclusion. TRPV4 channels expressed on alveolar macrophages are involved in the inflammatory process and airway remodeling in COPD, which is manifested by their relationships with the level of certain cytokines production, as well as the rate of the progression of bronchial obstruction.","PeriodicalId":9598,"journal":{"name":"Bulletin Physiology and Pathology of Respiration","volume":"280 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76891771","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
Prediction of uncontrolled course of bronchial asthma in children based on polymorphisms of genes of signaling molecules of the immune system and detoxification genes 基于免疫系统和解毒基因信号分子基因多态性预测儿童支气管哮喘不可控病程
Pub Date : 2022-12-22 DOI: 10.36604/1998-5029-2022-86-56-61
E. Suprun
Aim. To study the possibility of predicting the asthma control at various stages of the development of the disease, possibly on the basis of taking into account the genetic polymorphisms of Toll-like receptors, cytokines and detoxification system genes using the statistical method of learning neural networks.Materials and methods. We ex­amined 167 children with bronchial asthma. The degree of asthma control was determined, the following mutations were detected: TLR2-Arg753Glu, TLR4-Asp299Gly, TLR4-Ghr399Ile, TLR9-T1237C, TLR9-A2848G; IL4-C589T, IL6- C174G, IL10-G1082A, IL10-C592A, IL10-C819T, IL12B-A1188C, TNFa-G308A; GSTM, GSTT, GSTM/GSTT, GSTP1 Ile105Val, GSTP1 Ala114Val, by PCR. The STATISTICA Automated Neural Networks package was used to model neural networks.Results. The model is based on the MLP (15-9-3) multilayer perceptron architecture with a layer of 15 input neurons (by the number of analyzed variables), a hidden intermediate layer of 9 neurons and an output layer of 3 neurons by the number of values of the classified variable (control). The training algorithm was chosen by BFGS as the most adequate to the classification task. The error function is traditionally chosen as the sum of squared deviations. The activation function of output neurons is Softmax. The activation function of the intermediate layer is hyperbolic. The volume of the training sample was 88 sets. The volume of samples for testing and quality control of the model was 36 sets. The resulting model was able to predict 79.01% of the correct values of the target variable (the degree of asthma control).Conclusion. The application of the developed program makes it possible to predict the possibility of uncontrolled or partially controlled asthma at any stage of the disease, including preclinical and pre-nosological for groups with a high risk of asthma. This allows you to individually adjust the measures of secondary and even primary prevention of asthma within the personal­ization of therapeutic approaches.
的目标。研究利用学习神经网络的统计方法,在考虑toll样受体、细胞因子和解毒系统基因遗传多态性的基础上,预测疾病发展各阶段哮喘控制的可能性。材料和方法。我们检查了167名患有支气管哮喘的儿童。测定哮喘控制程度,检测到以下突变:TLR2-Arg753Glu、TLR4-Asp299Gly、TLR4-Ghr399Ile、TLR9-T1237C、TLR9-A2848G;IL4-C589T、IL6- C174G、IL10-G1082A、IL10-C592A、IL10-C819T、IL12B-A1188C、TNFa-G308AGSTM, GSTT, GSTM/GSTT, GSTP1 Ile105Val, GSTP1 Ala114Val,通过PCR。使用STATISTICA自动化神经网络软件包对神经网络进行建模。该模型基于MLP(15-9-3)多层感知器架构,其中一层有15个输入神经元(由被分析变量的数量决定),一个隐藏的中间层有9个神经元,一个输出层有3个神经元(由分类变量的值决定)。BFGS选择了最适合分类任务的训练算法。传统上选择误差函数为偏差平方和。输出神经元的激活函数为Softmax。中间层的激活函数是双曲的。训练样本的体积为88组。该模型用于检测和质量控制的样本量为36套。所建立的模型预测目标变量(哮喘控制程度)的正确率为79.01%。开发的程序的应用使得在疾病的任何阶段预测不受控制或部分控制的哮喘的可能性成为可能,包括对哮喘高风险群体的临床前和疾病前。这使您可以在个性化治疗方法中单独调整哮喘的二级甚至一级预防措施。
{"title":"Prediction of uncontrolled course of bronchial asthma in children based on polymorphisms of genes of signaling molecules of the immune system and detoxification genes","authors":"E. Suprun","doi":"10.36604/1998-5029-2022-86-56-61","DOIUrl":"https://doi.org/10.36604/1998-5029-2022-86-56-61","url":null,"abstract":"Aim. To study the possibility of predicting the asthma control at various stages of the development of the disease, possibly on the basis of taking into account the genetic polymorphisms of Toll-like receptors, cytokines and detoxification system genes using the statistical method of learning neural networks.Materials and methods. We ex­amined 167 children with bronchial asthma. The degree of asthma control was determined, the following mutations were detected: TLR2-Arg753Glu, TLR4-Asp299Gly, TLR4-Ghr399Ile, TLR9-T1237C, TLR9-A2848G; IL4-C589T, IL6- C174G, IL10-G1082A, IL10-C592A, IL10-C819T, IL12B-A1188C, TNFa-G308A; GSTM, GSTT, GSTM/GSTT, GSTP1 Ile105Val, GSTP1 Ala114Val, by PCR. The STATISTICA Automated Neural Networks package was used to model neural networks.Results. The model is based on the MLP (15-9-3) multilayer perceptron architecture with a layer of 15 input neurons (by the number of analyzed variables), a hidden intermediate layer of 9 neurons and an output layer of 3 neurons by the number of values of the classified variable (control). The training algorithm was chosen by BFGS as the most adequate to the classification task. The error function is traditionally chosen as the sum of squared deviations. The activation function of output neurons is Softmax. The activation function of the intermediate layer is hyperbolic. The volume of the training sample was 88 sets. The volume of samples for testing and quality control of the model was 36 sets. The resulting model was able to predict 79.01% of the correct values of the target variable (the degree of asthma control).Conclusion. The application of the developed program makes it possible to predict the possibility of uncontrolled or partially controlled asthma at any stage of the disease, including preclinical and pre-nosological for groups with a high risk of asthma. This allows you to individually adjust the measures of secondary and even primary prevention of asthma within the personal­ization of therapeutic approaches.","PeriodicalId":9598,"journal":{"name":"Bulletin Physiology and Pathology of Respiration","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74271841","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
Airway neutrophils and myeloperoxidase in asthma patients with cold-induced bronchoconstriction 哮喘冷致支气管缩窄患者气道中性粒细胞和髓过氧化物酶的变化
Pub Date : 2022-12-22 DOI: 10.36604/1998-5029-2022-86-40-49
A. Pirogov, A. Prikhodko, J. Perelman
Introduction. The role of neutrophil inflammation of the bronchi in patients with asthma in the devel­opment and manifestation of cold airway hyperresponsiveness (CAHR) has not been sufficiently studied.Aim. To assess the level of neutrophils and the activity of myeloperoxidase (MPO) in the bronchi of asthma patients with cold-induced bronchospasm.Materials and methods. In 138 patients with mild-to-moderate asthma with CAHR, the level of asthma control (ACT), lung function (FEV1), cellular composition of sputum was examined before and after the bronchoprovo­cation test by isocapnic hyperventilation with cold air (IHCA). In sputum samples, the percentage of neutrophils, eosino­phils, and bronchial epithelial cells (structurally intact cylindrical ciliated and goblet cells) was assessed; the concentration and activity of MPO in neutrophils were studied by the cytochemical method.Results. The patients were divided into three groups: group 1 (n=94) - patients with mild cold-induced bronchospasm, group 2 (n=28) - with moderate broncho­spasm, group 3 (n=16) - with severe bronchospasm (AFEV1=- 13.5±0.3, -24.6±0.5, -36.9±1.5%, respectively). Patients did not differ in the level of asthma control (16 [12; 21]; 16 [13; 20] and 16 [12; 21] ACT points, respectively). Patients of the third group had lower values of bronchial patency in comparison with the first and second groups: FEV1 79.4±3.2; 92.4±1.7 (p<0.01); 92.1±2.9% and FEF25-75 46.4±4.3; 66.1±2.5 (p<0.001); 63.2±4.0% (p<0.01). In sputum after the IHCA test in groups 2 and 3, an increase in the number of neutrophils was recorded from 35.5±3.9 to 46.0±3.8% (p<0.05) and from 39.0±3.8 to 52, 4±4.4% (p<0.05), respectively, while the number of neutrophils in group 1 did not change (43.2±2.4 and 44.3±2.1%). The concentration of MPO in response to the IHCA test in all groups significantly increased by more than 30% (p<0.05).Conclusion. The mobilization of neutrophils in a mixed pattern of airway inflammation in asthma pa­tients is associated with worsening of cold-induced bronchospasm. An increase in the content of MPO in neutrophil gran­ules in response to the action of cold air is aimed at enhancing the secretion of the enzyme in the interstitium, activating its oxidative activity in the respiratory tract, and escalating the oxidative/halogenating stress that accompanies broncho­spasm.
介绍。哮喘患者支气管中性粒细胞炎症在气道冷性高反应性(CAHR)发生和表现中的作用尚未得到充分研究。目的:探讨哮喘合并冷致支气管痉挛患者支气管中性粒细胞水平和髓过氧化物酶(MPO)活性的变化。材料和方法。对138例轻中度哮喘合并CAHR患者,采用冷风异氧过度通气(IHCA)支气管刺激试验前后,分别检测哮喘控制水平(ACT)、肺功能(FEV1)、痰细胞组成。在痰样本中,评估中性粒细胞、嗜酸性粒细胞和支气管上皮细胞(结构完整的圆柱形纤毛细胞和杯状细胞)的百分比;用细胞化学方法研究了中性粒细胞中MPO的浓度和活性。将患者分为3组:1组(n=94)为轻度冷致支气管痉挛,2组(n=28)为中度支气管痉挛,3组(n=16)为重度支气管痉挛(AFEV1分别为- 13.5±0.3、-24.6±0.5、-36.9±1.5%)。患者的哮喘控制水平无差异(16 [12;21);16 [13;[20]和[12];[21] ACT分)。第三组患者支气管通畅值低于第一组和第二组:FEV1 79.4±3.2;92.4±1.7 (p < 0.01);FEF25-75为46.4±4.3;66.1±2.5 (p < 0.001);63.2±4.0% (p < 0.01)。在IHCA试验后的痰液中,2组和3组的中性粒细胞数量分别从35.5±3.9增加到46.0±3.8% (p<0.05)和从39.0±3.8增加到52.4±4.4% (p<0.05),而1组中性粒细胞数量没有变化(43.2±2.4和44.3±2.1%)。各组对IHCA试验反应后MPO浓度均显著升高30%以上(p<0.05)。哮喘患者气道炎症混合型中性粒细胞的动员与冷致支气管痉挛的恶化有关。中性粒细胞颗粒中MPO含量的增加是对冷空气作用的反应,其目的是增强间质酶的分泌,激活其在呼吸道的氧化活性,并加剧伴随支气管痉挛的氧化/卤化应激。
{"title":"Airway neutrophils and myeloperoxidase in asthma patients with cold-induced bronchoconstriction","authors":"A. Pirogov, A. Prikhodko, J. Perelman","doi":"10.36604/1998-5029-2022-86-40-49","DOIUrl":"https://doi.org/10.36604/1998-5029-2022-86-40-49","url":null,"abstract":"Introduction. The role of neutrophil inflammation of the bronchi in patients with asthma in the devel­opment and manifestation of cold airway hyperresponsiveness (CAHR) has not been sufficiently studied.Aim. To assess the level of neutrophils and the activity of myeloperoxidase (MPO) in the bronchi of asthma patients with cold-induced bronchospasm.Materials and methods. In 138 patients with mild-to-moderate asthma with CAHR, the level of asthma control (ACT), lung function (FEV1), cellular composition of sputum was examined before and after the bronchoprovo­cation test by isocapnic hyperventilation with cold air (IHCA). In sputum samples, the percentage of neutrophils, eosino­phils, and bronchial epithelial cells (structurally intact cylindrical ciliated and goblet cells) was assessed; the concentration and activity of MPO in neutrophils were studied by the cytochemical method.Results. The patients were divided into three groups: group 1 (n=94) - patients with mild cold-induced bronchospasm, group 2 (n=28) - with moderate broncho­spasm, group 3 (n=16) - with severe bronchospasm (AFEV1=- 13.5±0.3, -24.6±0.5, -36.9±1.5%, respectively). Patients did not differ in the level of asthma control (16 [12; 21]; 16 [13; 20] and 16 [12; 21] ACT points, respectively). Patients of the third group had lower values of bronchial patency in comparison with the first and second groups: FEV1 79.4±3.2; 92.4±1.7 (p<0.01); 92.1±2.9% and FEF25-75 46.4±4.3; 66.1±2.5 (p<0.001); 63.2±4.0% (p<0.01). In sputum after the IHCA test in groups 2 and 3, an increase in the number of neutrophils was recorded from 35.5±3.9 to 46.0±3.8% (p<0.05) and from 39.0±3.8 to 52, 4±4.4% (p<0.05), respectively, while the number of neutrophils in group 1 did not change (43.2±2.4 and 44.3±2.1%). The concentration of MPO in response to the IHCA test in all groups significantly increased by more than 30% (p<0.05).Conclusion. The mobilization of neutrophils in a mixed pattern of airway inflammation in asthma pa­tients is associated with worsening of cold-induced bronchospasm. An increase in the content of MPO in neutrophil gran­ules in response to the action of cold air is aimed at enhancing the secretion of the enzyme in the interstitium, activating its oxidative activity in the respiratory tract, and escalating the oxidative/halogenating stress that accompanies broncho­spasm.","PeriodicalId":9598,"journal":{"name":"Bulletin Physiology and Pathology of Respiration","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76618274","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
Method for lung inflation determining in asthma patients with osmotic airway hyperresponsiveness 渗透性气道高反应性哮喘患者肺充气测定方法
Pub Date : 2022-12-22 DOI: 10.36604/1998-5029-2022-86-62-67
E. Afanas'eva
Aim. To develop a method for determining the lung inflation by the indexes of forced expiratory flow­volume spirometry.Materials and methods. In 43 patients with mild persistent uncontrolled asthma in combination with osmotic airway hyperresponsiveness, the lung function indexes were assessed by spirometry using a bronchodilation test and bodyplethysmography.Results. From the entire set of parameters, using regression analysis, two equations were con­structed, with the inclusion of the main spirometric indicators (FEV1 in % of the due value, AFEVt and AFEF75 after the bronchodilation test, in %). The equations obtained make it possible to calculate lung inflation indices in asthma patients with osmotic airway hyperresponsiveness to select patients for referral for bodyplethysmography and multispiral computed tomography of the lungs in order to diagnose the severity of hyperinflation.Conclusion. The developed regression models provide an opportunity for a preliminary assessment of the presence and degree of lung hyperinflation in asthma patients with osmotic airway hyperresponsiveness, to determine personal approaches to basic anti-inflammatory therapy and, if necessary, to correct it in a timely manner.
的目标。目的:建立用力呼气流量-容积肺活量法测定肺充气的方法。材料和方法。对43例合并渗透性气道高反应性的轻度持续性不受控制哮喘患者,采用肺活量测定法、支气管扩张试验和体体积描记术评估肺功能指标。从整个参数集出发,采用回归分析,构建两个方程,其中包括主要肺活量指标(FEV1占应有值的%,支气管舒张试验后AFEVt和AFEF75占应有值的%)。所得公式可用于计算渗透性气道高反应性哮喘患者的肺充气指数,以选择转诊患者进行肺体积脉搏图和肺部多螺旋ct检查,以诊断高充气的严重程度。建立的回归模型为初步评估渗透性气道高反应性哮喘患者的肺部过度膨胀的存在和程度提供了机会,从而确定基本抗炎治疗的个人方法,并在必要时及时纠正。
{"title":"Method for lung inflation determining in asthma patients with osmotic airway hyperresponsiveness","authors":"E. Afanas'eva","doi":"10.36604/1998-5029-2022-86-62-67","DOIUrl":"https://doi.org/10.36604/1998-5029-2022-86-62-67","url":null,"abstract":"Aim. To develop a method for determining the lung inflation by the indexes of forced expiratory flow­volume spirometry.Materials and methods. In 43 patients with mild persistent uncontrolled asthma in combination with osmotic airway hyperresponsiveness, the lung function indexes were assessed by spirometry using a bronchodilation test and bodyplethysmography.Results. From the entire set of parameters, using regression analysis, two equations were con­structed, with the inclusion of the main spirometric indicators (FEV1 in % of the due value, AFEVt and AFEF75 after the bronchodilation test, in %). The equations obtained make it possible to calculate lung inflation indices in asthma patients with osmotic airway hyperresponsiveness to select patients for referral for bodyplethysmography and multispiral computed tomography of the lungs in order to diagnose the severity of hyperinflation.Conclusion. The developed regression models provide an opportunity for a preliminary assessment of the presence and degree of lung hyperinflation in asthma patients with osmotic airway hyperresponsiveness, to determine personal approaches to basic anti-inflammatory therapy and, if necessary, to correct it in a timely manner.","PeriodicalId":9598,"journal":{"name":"Bulletin Physiology and Pathology of Respiration","volume":"55 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81382620","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
Assessment of the membrane potential of mitochondria in immunocompetent blood cells of children with asthma, depending on controllability of the course of the disease 哮喘儿童免疫能力血细胞中线粒体膜电位的评估,取决于疾病进程的可控性
Pub Date : 2022-12-22 DOI: 10.36604/1998-5029-2022-86-50-55
E. Suprun
Aim. To study the functional state of immunocompetent blood cells by assessing the membrane potential of mitochondria (MPM) in bronchial asthma in children, depending on the controllability of the course of the disease.Materials and methods. 167 children suffering from asthma aged from 1 to 17 years were examined, two groups were formed: 1 - controlled course of asthma (n=70), 2 - partially controlled and uncontrolled course of asthma (n=97). The functional and energetic status of immunocompetent blood cells was assessed by flow cytometry with determination of MPM using JC-1 dye.Results. The proportion of cells with reduced MPM in children with asthma in comparison with conditionally healthy children is higher in all pools - lymphocytes (46.1% vs. 34.0%), monocytes (12.0% vs. 9.0%), gran­ulocytes (11.3% vs. 7.0%). A higher percentage of cells with reduced MPM was found in the pools of monocytes (15.4% vs. 8.8%) and granulocytes (13.8% vs. 6.7%) with uncontrolled asthma. “Method for a comprehensive assessment of the energy security of immunocompetent blood cells” has been developed and patented. According to this method, the degrees of energy deficiency are relevant to the control of the course of asthma: in group 1, there is no energy deficit in 12.9% of cases, the first degree of deficiency in 40%, the second in 20%, the third in 27.1%; in the second group - 11,3%, 15,5%, 42,2%, 31,0% accordingly.Conclusion. The use of the developed method for a comprehensive assessment of the energy security of immunocompetent blood cells as an additional method to the approved medical standards, technically performed in a short time and with high accuracy, makes it possible to conduct early preclinical diagnostics of energy-deficient con­ditions of immunocompetent blood cells in asthma; according to the degree of disturbances detected, it is reasonable to determine the choice, the amount of necessary therapy and evaluate the effectiveness of treatment.
的目标。通过评估线粒体膜电位(MPM)来研究儿童支气管哮喘免疫活性血细胞的功能状态,这取决于疾病过程的可控性。材料和方法。对167例1 ~ 17岁哮喘患儿进行调查,分为哮喘控制期1组(n=70)和哮喘部分控制和不控制期2组(n=97)。流式细胞术检测免疫活性血细胞的功能和能量状态,用JC-1染料测定MPM。与条件健康儿童相比,哮喘儿童MPM降低的细胞比例在所有池中都更高——淋巴细胞(46.1%比34.0%)、单核细胞(12.0%比9.0%)、粒细胞(11.3%比7.0%)。在未控制哮喘的单核细胞池(15.4%对8.8%)和粒细胞池(13.8%对6.7%)中发现MPM降低的细胞比例较高。“免疫能力血细胞能量安全综合评估方法”已研制成功并获得专利。根据该方法,能量不足程度与哮喘病程的控制有关:1组无能量不足12.9%,1级不足40%,2级不足20%,3级不足27.1%;第二组分别为11.3%、15.5%、42.2%、31.0%。将所开发的方法用于全面评估免疫能力血细胞的能量安全,作为已批准的医疗标准的一种附加方法,在短时间内技术上执行,具有很高的准确性,从而可以对哮喘中免疫能力血细胞的能量缺乏情况进行早期临床前诊断;根据检测到的干扰程度,合理确定治疗的选择、必要治疗的量和评估治疗的有效性。
{"title":"Assessment of the membrane potential of mitochondria in immunocompetent blood cells of children with asthma, depending on controllability of the course of the disease","authors":"E. Suprun","doi":"10.36604/1998-5029-2022-86-50-55","DOIUrl":"https://doi.org/10.36604/1998-5029-2022-86-50-55","url":null,"abstract":"Aim. To study the functional state of immunocompetent blood cells by assessing the membrane potential of mitochondria (MPM) in bronchial asthma in children, depending on the controllability of the course of the disease.Materials and methods. 167 children suffering from asthma aged from 1 to 17 years were examined, two groups were formed: 1 - controlled course of asthma (n=70), 2 - partially controlled and uncontrolled course of asthma (n=97). The functional and energetic status of immunocompetent blood cells was assessed by flow cytometry with determination of MPM using JC-1 dye.Results. The proportion of cells with reduced MPM in children with asthma in comparison with conditionally healthy children is higher in all pools - lymphocytes (46.1% vs. 34.0%), monocytes (12.0% vs. 9.0%), gran­ulocytes (11.3% vs. 7.0%). A higher percentage of cells with reduced MPM was found in the pools of monocytes (15.4% vs. 8.8%) and granulocytes (13.8% vs. 6.7%) with uncontrolled asthma. “Method for a comprehensive assessment of the energy security of immunocompetent blood cells” has been developed and patented. According to this method, the degrees of energy deficiency are relevant to the control of the course of asthma: in group 1, there is no energy deficit in 12.9% of cases, the first degree of deficiency in 40%, the second in 20%, the third in 27.1%; in the second group - 11,3%, 15,5%, 42,2%, 31,0% accordingly.Conclusion. The use of the developed method for a comprehensive assessment of the energy security of immunocompetent blood cells as an additional method to the approved medical standards, technically performed in a short time and with high accuracy, makes it possible to conduct early preclinical diagnostics of energy-deficient con­ditions of immunocompetent blood cells in asthma; according to the degree of disturbances detected, it is reasonable to determine the choice, the amount of necessary therapy and evaluate the effectiveness of treatment.","PeriodicalId":9598,"journal":{"name":"Bulletin Physiology and Pathology of Respiration","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89293352","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
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Bulletin Physiology and Pathology of Respiration
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