Dynamics of the chemokine ENA-78/CXCL5 levels in blood serum and skin exudate in patients with atopic dermatitis

Currently, there are only scarce data on dynamics of biologically active substances in the lesions associated with atopic dermatitis. Persistence of microorganisms in atopic dermatitis is high on the skin surface. However, pathophysiological significance of ENA-78/CXCL5 for development of atopic dermatitis was not studied so far. The ENA-78/CXCL5 is known to be produced by endotheliocytes, keratinocytes, eosinophils, fibroblasts to activate neutrophil migration, especially under the influence of LPS-containing microorganisms. The aim of this study was to evaluate the dynamics of ENA-78/CXCL5 chemokine levels in blood serum and skin exudates in the patients with atopic dermatitis, as well as to determine pathophysiological role of the chemokine in pathogenesis of dermatosis. 80 patients with limited and widespread forms of atopic dermatitis and 15 volunteers were under observation. The dynamics of ENA-78/CXCL5 levels was studied in blood sera and skin exudates. Blood samples for the study were drawn at the time periods of exacerbation and remission. Skin exudates were taken from the patients during the exacerbation period using disposable insulin syringes and 20-G disposable needles. In healthy volunteers, the skin exudate was obtained by the “skin window” technique as described by V.V. Klimov and coauthors “A method for assessing minimal inflammatory activity of skin in atopic dermatitis in remission”. The cell analysis was conducted by flow cytofluorimetry using the LEGEND plex TM Human Proinflammatory Chemokine Panel (USA) according to the manufacturer’s protocol. Serum concentrations of chemokine ENA-78/CXCL5 in adolescents with atopic dermatitis, exceeded the range for healthy volunteers. During remission of dermatitis, the chemokine level did not reach the indices in the control group. In adults, the ENA-78/CXCL5 concentration, both at the onset of symptoms and upon their resolution, was below the control levels. Maximal concentrations of ENA-78/CXCL5 chemokine were detected in the skin exudates. As based on our data on the dynamics of ENA-78/CXCL5 chemokine levels, it could be assumed that this substance may represent a sufficient link in pathogenesis of atopic dermatitis, by causing migration of neutrophils and monocytes to the affected area. The ENA-78/CXCL5 chemokine may be a marker of microbial pathogenesis and cellular damage in atopic dermatitis

Time course of autoantibodies to collagen type I and III in blood serum and skin exudate in atopic dermatitis

In accordance with Clinical Guidelines of the Russian Society of Dermatovenerologists and Cosmetologists, atopic dermatitis is a chronic allergic genetically determined dermatosis of a multifactorial nature. There are, however, some aspects that challenge the allergic nature of dermatosis. For example, according to literature data, not all the patients have increased synthesis of immunoglobulin E, some of them are torpid to antihistamine treatment, and, when examining the skin of some patients with atopic dermatitis, an absolute polymorphism of rashes is revealed, thus being not typical to the reagin-type allergic reactions. According to modern data, autoimmune theory is assumed for the mechanisms of atopic dermatitis. However, objective proofs of this theory have not been presented, thus drawing our attention to the studies of this issue. The aim of this study was to identify autoimmune pathogenetic mechanisms of atopic dermatitis. The study included 40 adolescents and 40 adult patients with limited and extended forms of atopic dermatitis. The patients were evaluated during the period of exacerbation and remission of the disease. Blood and skin exudates samples were taken from all the patients. The control group consisted of 30 practically healthy volunteers in whom skin exudate was obtained by the “skin window” technique as proposed by Klimov V.V. et al. “A method for assessing minimal inflammatory activity of skin in atopic dermatitis in remission”. Concentrations of IgG autoantibodies to collagen types I and III were determined in blood serum and skin exudate samples applying ELISA techniques with ready-made panels AEA571Hu ELISA Kit for Anti-Collagen Type I Antibody (USA), AEA176Hu ELISA Kit for Anti-Collagen Type III Antibody (USA), according to the manufacturer’s protocols. For the first time, the contents of autoantibodies to skin collagen types I and III in the patients with atopic dermatitis we studied in parallel, i.e., at systemic level and in affected skin. If compared to the group of healthy volunteers, the concentration of autoantibodies to collagen types I and III was found to be increased in all the patients with atopic dermatitis, both during exacerbation and in remission of the disease. The maximal values of autoantibodies to collagen types I and III were recorded in blood serum upon development of clinical symptoms of dermatosis, along with low contents of these antibodies detectable in their skin exudates. Permanently high concentrations of autoantibodies to collagen types I and III in blood serum at exacerbation and remission of atopic dermatitis, and their low level in their skin exudate suggest emergence of circulating and precipitating immune complexes, thus allowing us to consider atopic dermatitis as an autoimmune process

Pathophysiological role of chemokine MIG/CXCL9 in the development of atopic dermatitis

Background. In patients with atopic dermatitis, the persistence of microorganisms on the skin surface is high, which can enhance the expression of MIG/CXCL9, exacerbating inflammation and activating keratinocyte apoptosis, however, the dynamics of this chemokine in atopic dermatitis has not been studied.The aim. To study the concentration of chemokine MIG/CXCL9 in the dynamics of atopic dermatitis and determine its role in the pathogenesis of dermatosis.Materials and methods. The study included 80 patients aged 13 to 44 years with limited and widespread atopic dermatitis and 30 practically healthy volunteers. The therapy of patients, the collection of biological material were carried out in the Regional Dermatovenerologic Dispensary in Chita, laboratory tests were performed at the Chita State Medical Academy in the period from 2018 to 2020. The MIG/CXCL9 level was studied during exacerbation and remission of the disease in blood serum and skin exudate by flow cytofluorimetry using LEGENDplex Human Proinflammatory Chemokine Panel (BioLegend, USA). In healthy volunteers, skin exudate sampling was carried out by the “skin window” method. For statistical processing, the Microsoft Excel (Microsoft Corp., USA) application software package and SPSS Statistics 25.0 (IBM Corp., USA) were used.Results. The concentration of chemokine MIG/CXCL9 in the skin exudate is greater than in the blood serum. With a limited form of the disease in adolescents, the level of MIG/CXCL9 in the skin exudate is 8.1 times higher than the control values, with a common form – 9.3 times. In adults with advanced atopic dermatitis, the concentration of chemokine IL/CXCL9 in the skin exudate is 20.8 times higher than the values of the control group.Conclusion. In atopic dermatitis, the level of chemokine MIG/CXCL9 is higher in the cutaneous pathological process. In the pathogenesis of the disease, MIG/ CXCL9 inhibits collagen synthesis and promotes apoptosis of keratinocytes, followed by the formation of hyperreactivity of the skin, its dryness and peeling

Functional activity of the oral endothelium in persons, with chronic periodontitis during treatment with plasmolifting

Chronic periodontitis as an osteoimmune disease of the oral cavity is accompanied by a change in the functional activity of endotheliocytes. Moreover, abnormal vascularization exacerbates periodontal inflammation, as it promotes the transmigration of a larger number of immunocompetent cells, the influx of inflammatory mediators and cytokines.The aim of our work was to study the functional activity of the endothelium of the vessels of the oral cavity in persons suffering from chronic periodontitis in the treatment of plasmolifting.Materials and methods. Under observation were 30 patients diagnosed with chronic generalized periodontitis of moderate severity at the age of 35 (32.50; 40.00) years, with no severe somatic pathology (main group). The comparison group included 20 people aged 38 (34.00; 45.00) years with no inflammatory diseases in the oral cavity. All patients underwent local anti-inflammatory therapy and sanitation of periodontal pockets, correction of occlusal contacts, curettage, plasma lifting. Oral fluid concentration of soluble adhesion molecules ICAM-1 and VCAM-1, endothelin-1, qualitative and quantitative composition of microflora were determined.Results. After the treatment with plasmolifting, a noticeable relief of the activity of the inflammatory process was observed. In patients with chronic periodontitis, Porphyromonas gingivalis was found in 100 % of cases in a titer of 5.73 (4.9; 6.7) lg (gEq/sample), in 62.5 % – Prevotella intermedia in a titer of 4.5 (3.0; 5.5) lg (gEq/sample). Against the background of therapy, decrease of the occurrence of the microorganism and of the number of microorganisms was observed. The concentration of the soluble form of VCAM-1 in the oral fluid of patients with chronic periodontitis exceeded the values of the control group by 38.3 times (p = 0.000001), and ICAM-1 – by 18.1 times (p = 0.00001). Against the background of plasmolifting therapy, the level of the studied substances decreased, but exceeded the control values by 25.2 and 6.4 times, respectively. The content of endothelin in the oral fluid in patients with periodontitis exceeded the values of healthy individuals by 40.7 % (p = 0.003), during therapy its values decreased, but did not reach the level of healthy volunteers (p = 0.04)

Взаимосвязь некоторых параметров мукозального иммунитета полости рта с уровнем витамина D у пациентов с множественным кариесом

Aim. To determine the saliva level of immunoregulatory proteins in patients with rampant caries and 25-hydroxyvitamin D (25(OH)D) deficiency and evaluate the association of their concentration with 25(OH)D plasma level.Materials and methods. The study was performed in two groups. The experimental group included 15 patients aged 20–22 years with rampant caries and the 25(OH)D plasma level of < 20 ng / ml. The control group encompassed 15 healthy age-matched volunteers with the 25(OH)D plasma level of 20–100 ng / ml. The concentrations of B7.2 (CD86), free active TGF-β1, CTLA-4, PD-1, Tim-3, LAG-3, IGFBP-4, and ICAM-1 were assessed using flow cytometry. The levels of LL-37 and secretory immunoglobulin A (sIgA) were measured using ELISA. The Spearman’s rank correlation coefficient was used to reveal a correlation between the indicated proteins and the 25(OH)D plasma level.Results. A decrease in B7.2 (CD86), PD-1, Tim-3, sIgA, and LL-37 and elevation of IGFBP-4 and ICAM-1 saliva levels were detected in patients with rampant caries and 25-hydroxyvitamin D deficiency. A positive Spearman’s rank correlation coefficient was revealed between plasma 25(OH)D and saliva levels of free active TGF-β1, CTLA4, B7.2 (CD86), LL-37, and sIgA. A negative correlation was revealed between 25(OH)Dand ICAM-1.Conclusion. 25(OH)D deficiency in patients with rampant caries is associated with decreased levels of B7.2 (CD86), PD-1, Tim-3, sIgA, and LL-37 and elevated levels of IGFBP-4 and ICAM-1 in the saliva. Цель – оценить содержание иммунорегуляторных молекул в слюне у лиц с множественным кариесом и дефицитом 25(OH)D3 и определить взаимосвязи их величин с концентрацией 25(OH)D3 в крови.Материалы и методы. Обследованы две группы лиц в возрасте 20–22 лет. В одну включены 15 человек с кариесом и уровнем 25(OH)D3 менее 20 нг/мл, в другую (контрольную) – 15 здоровых человек с содержанием 25(OH)D3 30–100 нг/мл. В ротовой жидкости определены концентрации растворимых форм молекул B7.2 (CD86), Free Active TGF-b1, CTLA-4, PD-1, Tim-3, LAG-3, IGFBP-4, ICAM-1 методом проточной цитофлуометрии, количество кателицидина LL-37, секреторного иммуноглобулина A (IgA) методом иммуноферментного анализа. Между определяемыми показателями рассчитан критерий корреляции Спирмена.Результаты. У лиц с кариесом и дефицитом витамина D выявлено снижение значений Free Active TGF-b1, B7.2 (CD86), PD-1, Tim-3, sIgA, кателицидина LL-37 и повышение уровня IGFBP-4 и ICAM-1 в слюне. Обнаружено наличие прямых корреляционных связей между количеством 25(OH)D3 в крови, с одной стороны, и значениями Free Active TGF-b1, CTLA-4, В7.2 (CD86), секреторного IgA, пептида LL-37 – с другой. Зафиксирована отрицательная взаимосвязь между величинами 25(OH)D3 и ICAM-1.Заключение. На фоне дефицита витамина D при множественном кариесе в ротовой жидкости регистрируются низкие концентрации Free Active TGF-b1, B7.2 (CD86), PD-1, Tim-3, секреторного IgA, кателицидина LL-37 по сравнению с контролем, но увеличены значения IGFBP-4 и ICAM-1.

SIGNIFICANCE OF THE SPHINGOMYELIN CHANGES IN CORD BLOOD LYMPHOCYTES FOR THE ACTIVITY OF CENTRAL NERVOUS SYSTEM IN PRETERM NEWBORNS

Abstract. Different neuropsychical pathologies are revealed in preterm infants during the subsequent stages of ontogenesis. Violation of the phospholipids composition of cell membranes is one of the essential pathogenetic mechanisms of the psychoneurological pathology.Objective: to study the content of phospholipid fractions of cord blood lymphocytes in preterm infants at different gestation terms.The spectrum of phospholipids was determined by thin layer chromatography in 39 healthy full-term newborns and in 65 preterm children (28-36 weeks). We revealed an increased content of sphingomyelin in cord blood lymphocytes in preterm infants. The highest rates were found in children with a gestation term of less than 32 weeks (p = 0.004 compared with full-term infants). Sphingomyelin, unlike other phospholipids of cell membranes, is concentrated mainly in the brain, which indicates its special role for CNS activity.Recently, there has been formed the idea on the importance of lipid components of fat globule membranes of breast milk for optimal neurological development of children. Given the changes in the sphingomyelin content in the cell membranes of preterm newborns and its important structural and functional role for CNS activity, we believe that special attention should be paid to its content in the formulas for preterm infants among standard components

Effect of helium presence on tungsten-deuterium co-deposited films

Co-deposited W-D, W-He, and mixed W-D-He films 250 nm thick were investigated. The films were obtained by magnetron sputtering of W in Ar:D2:He =: 1:1:0, 1:0:1, 1:1:0.05, and 1:1:0.2, gas mixtures and at deposition temperatures of ∼ 350 K, 500 K, and 800 K. The films were studied by thermal desorption spectroscopy (TDS) with Tmax = 2200 K using threshold ionization mass spectrometry to separate D2 and He signals. It was found that films obtained in gas mixtures with mixed He-D2 atmospheres contained less total gas atoms than films deposited in pure D2 or He atmospheres. It was found that in mixed W-D-He films, He trapping with high binding energies (Tdes > 1500 K) is strongly mitigated

First study of lithium boron composite as plasma facing material

Lithium-Boron Composite Material (LBCM) is presented as a plasma-facing material with a lot of promise from the perspective of liquid metal first wall. LBCM consists of ∼ 20 w.% boron and ∼ 80 w.% lithium, arranged in the form of a Li5B4 matrix filled with metal lithium, similar to capillary porous systems (CPS) already used as plasma-facing elements. The characteristic matrix cell size is approximately 5 µm. LBCM was subjected to electron flux and helium plasma in a linear PR-2 device. LBCM maintained physical integrity up to T > 900 °C. Boron didn’t evaporate from LBCM under electron irradiation, but was sputtered during helium bombardment. CPS-like properties, wherein Li from the whole of the LBCM sample was transported to the area of the highest thermal load were observed